Updated on 2022/07/18

写真a

 
IWAMA Shintaro
 
Organization
Nagoya University Hospital Endocrinology and Diabetes Lecturer
Graduate School
Graduate School of Medicine
Title
Lecturer

Degree 1

  1. Doctor (Medical Science) ( 2009.9   Nagoya University ) 

Research Interests 4

  1. Autoimmune diseases

  2. Hypophysitis

  3. Hypophysitis

  4. autoantibody

Research Areas 3

  1. Life Science / Metabolism and endocrinology  / Endocrinology

  2. Others / Others  / 神経内分泌学

  3. Life Science / Immunology

Research History 6

  1. 名古屋大学医学部附属病院   糖尿病・内分泌内科   講師

    2020.4

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    Country:Japan

  2. 名古屋大学医学部附属病院   糖尿病・内分泌内科   病院講師

    2018.4 - 2020.3

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    Country:Japan

  3. 名古屋大学総合保健体育科学センター 講師

    2016.4 - 2018.3

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    Country:Japan

  4. 名古屋大学総合保健体育科学センター 特任講師

    2014.4 - 2016.3

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    Country:Japan

  5. 名古屋大学大学院医学系研究科 糖尿病・内分泌内科学

    2013.10 - 2014.3

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    Country:Japan

  6. Johns Hopkins University, Department of Pathology

    2011.3 - 2013.9

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    Country:Japan

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Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    2006.4 - 2009.9

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1996.4 - 2002.3

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    Country: Japan

Professional Memberships 8

  1. 日本内分泌学会   評議員、内分泌代謝科専門医、内分泌代謝科指導医

  2. 日本神経内分泌学会   評議員

  3. 日本内科学会   総合内科専門医

  4. 日本甲状腺学会   評議員

  5. 日本糖尿病学会   専門医

  6. Endocrine Society

  7. バゾプレシン研究会

  8. Society for Neuroscience

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Committee Memberships 6

  1. 日本内分泌学会   Endocrine Journal誌編集委員  

    2021.7   

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    Committee type:Academic society

  2. 日本内分泌学会   中堅若手の会(YEC)世話人  

    2021.4   

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    Committee type:Academic society

  3. 日本甲状腺学会   評議員  

    2018.11   

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    Committee type:Academic society

  4. 日本内分泌学会   免疫チェックポイント阻害薬による内分泌障害 ワーキンググループ委員  

    2018.4   

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    Committee type:Academic society

    <成果>免疫チェックポイント阻害薬による内分泌障害の診療ガイドライン
    https://www.jstage.jst.go.jp/article/endocrine/94/S.November/94_1/_article/-char/ja

  5. 日本神経内分泌学会   評議員  

    2016.10   

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    Committee type:Academic society

  6. 日本内分泌学会   評議員  

    2015.4   

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    Committee type:Academic society

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Awards 4

  1. 2020年度 日本甲状腺学会 第12回コスミック研究創成賞・優秀賞

    2020.11   日本甲状腺学会   抗PD-1抗体による破壊性甲状腺炎の発症に関与するリンパ球分画の同定

    岩間信太郎

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  2. 2020年度 第40回日本内分泌学会 研究奨励賞

    2020.7   日本内分泌学会   自己免疫と炎症が関与する視床下部下垂体疾患の研究

    岩間信太郎

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  3. 2020年度 第35回日本神経内分泌学会 川上賞

    2020.6   日本神経内分泌学会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  4. 2016年度(平成28年度) 名古屋大学医師会研究奨励賞

    2017.1   一般社団法人 名古屋大学医師会  

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    Country:Japan

 

Papers 71

  1. Protein Tyrosine Phosphatase 1B Deficiency Improves Glucose Homeostasis in Insulin-Dependent Diabetes Mellitus Treated with Leptin. Reviewed International journal

    Yoshihiro Ito, Runan Sun, Hiroshi Yagimuma, Keigo Taki, Akira Mizoguchi, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Taku Tsunekawa, Hiroshi Takagi, Daisuke Hagiwara, Shintaro Iwama, Hidetaka Suga, Hiroyuki Konishi, Hiroshi Kiyama, Hiroshi Arima, Ryoichi Banno

    Diabetes     2022.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    Leptin, a hormone secreted by adipocytes, exhibits therapeutic potential for the treatment of insulin-dependent diabetes mellitus (IDDM). Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme that negatively regulates leptin receptor signaling. Here, the role of PTP1B in the treatment of IDDM was investigated using PTP1B deficient (KO) mice and a PTP1B inhibitor. IDDM wild-type (WT) mice induced by streptozotocin showed marked hyperglycemia compared to non-IDDM WT mice. KO mice displayed significantly improved glucose metabolism equivalent to non-IDDM WT mice, whereas peripheral or central administration of leptin partially improved glucose metabolism in IDDM WT mice. Peripheral combination therapy of leptin and a PTP1B inhibitor in IDDM WT mice improved glucose metabolism to the same level as non-IDDM WT mice. Leptin was shown to act on the arcuate nucleus in the hypothalamus to suppress gluconeogenesis in liver and enhance glucose uptake in both brown adipose tissue and soleus muscle via the sympathetic nervous system. These effects were enhanced by PTP1B deficiency. Thus, treatment of IDDM with leptin, PTP1B deficiency or a PTP1B inhibitor was shown to enhance leptin activity in the hypothalamus to improve glucose metabolism. These findings suggest a potential alternative therapy for IDDM.

    DOI: 10.2337/db21-0953

    PubMed

  2. Immune checkpoint inhibitor-related thyroid dysfunction. Invited Reviewed

    Iwama S, Kobayashi T, Yasuda Y, Arima H

    Best practice & research. Clinical endocrinology & metabolism   Vol. 36 ( 3 ) page: 101660   2022.5

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Best Practice and Research: Clinical Endocrinology and Metabolism  

    Immune-related adverse events (irAEs) are caused by immune checkpoint inhibitors in several organs including the endocrine glands. Thyroid dysfunction (thyroid irAEs) is often observed among endocrine irAEs and is induced by blockade of programmed cell death 1 (PD-1), programmed death ligand 1, or PD-1 plus cytotoxic T-lymphocyte antigen 4. Endocrinologically, destructive thyroiditis or hypothyroidism is observed in most cases, whereas hyperthyroidism (Graves' disease) is rare. Most patients who develop destructive thyroiditis or hypothyroidism subsequently require thyroid hormone replacement therapy. Thyroid irAE development is associated with prolonged survival in patients with non-small cell lung carcinoma. The incidence of thyroid irAEs is higher in patients who are positive versus negative for anti-thyroid antibodies at baseline, suggesting that these antibodies can predict thyroid irAE development. Cytotoxic T cells, especially CD4 T cells, are reportedly involved in the development of destructive thyroiditis. In this review, we describe the clinical features, potential biomarkers, and mechanism of thyroid irAEs.

    DOI: 10.1016/j.beem.2022.101660

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  3. Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline Reviewed

    Iwama Shintaro, Kobayashi Tomoko, Yasuda Yoshinori, Okuji Takayuki, Ito Masaaki, Ando Masahiko, Zhou Xin, Yamagami Ayana, Onoue Takeshi, Kawaguchi Yohei, Miyata Takashi, Sugiyama Mariko, Takagi Hiroshi, Hagiwara Daisuke, Suga Hidetaka, Banno Ryoichi, Hase Tetsunari, Morise Masahiro, Wakahara Keiko, Yokota Kenji, Kato Masashi, Nishio Naoki, Tanaka Chie, Miyata Kazushi, Ogura Atsushi, Ito Takanori, Sawada Tsunaki, Shimokata Tomoya, Niimi Kaoru, Ohka Fumiharu, Ishigami Masatoshi, Gotoh Momokazu, Hashimoto Naozumi, Saito Ryuta, Kiyoi Hitoshi, Kajiyama Hiroaki, Ando Yuichi, Hibi Hideharu, Sone Michihiko, Akiyama Masashi, Kodera Yasuhiro, Arima Hiroshi

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   Vol. 107 ( 4 ) page: E1620 - E1630   2022.3

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/clinem/dgab829

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  4. Functional Lactotrophs in Induced Adenohypophysis Differentiated From Human iPS Cells Reviewed

    Miyake Natsuki, Nagai Takashi, Suga Hidetaka, Osuka Satoko, Kasai Takatoshi, Sakakibara Mayu, Soen Mika, Ozaki Hajime, Miwata Tsutomu, Asano Tomoyoshi, Kano Mayuko, Muraoka Ayako, Nakanishi Natsuki, Nakamura Tomoko, Goto Maki, Yasuda Yoshinori, Kawaguchi Yohei, Miyata Takashi, Kobayashi Tomoko, Sugiyama Mariko, Onoue Takeshi, Hagiwara Daisuke, Iwama Shintaro, Iwase Akira, Inoshita Naoko, Arima Hiroshi, Kajiyama Hiroaki

    ENDOCRINOLOGY   Vol. 163 ( 3 )   2022.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Endocrinology (United States)  

    Prolactin (PRL), a hormone involved in lactation, is mainly produced and secreted by the lactotrophs of the anterior pituitary (AP) gland. We previously reported a method to generate functional adrenocorticotropic hormone-producing cells by differentiating the AP and hypothalamus simultaneously from human induced pluripotent stem cells (iPSCs). However, PRL-producing cells in the induced AP have not been investigated. Here, we confirmed the presence of PRL-producing cells and evaluated their endocrine functions. We differentiated pituitary cells from human iPSCs using serum-free floating culture of embryoid-like aggregates with quick reaggregation (SFEB-q) method and evaluated the appearance and function of PRL-producing cells. Secretion of PRL from the differentiated aggregates was confirmed, which increased with further culture. Fluorescence immunostaining and immunoelectron microscopy revealed PRL-producing cells and PRL-positive secretory granules, respectively. PRL secretion was promoted by various prolactin secretagogues such as thyrotropin-releasing hormone, vasoactive intestinal peptide, and prolactin-releasing peptide, and inhibited by bromocriptine. Moreover, the presence of tyrosine hydroxylase-positive dopaminergic nerves in the hypothalamic tissue area around the center of the aggregates connecting to PRL-producing cells indicated the possibility of recapitulating PRL regulatory mechanisms through the hypothalamus. In conclusion, we generated pituitary lactotrophs from human iPSCs; these displayed similar secretory responsiveness as human pituitary cells in vivo. In the future, this is expected to be used as a model of human PRL-producing cells for various studies, such as drug discovery, prediction of side effects, and elucidation of tumorigenic mechanisms using disease-specific iPSCs. Furthermore, it may help to develop regenerative medicine for the pituitary gland.

    DOI: 10.1210/endocr/bqac004

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  5. Human Leukocyte Antigens and Biomarkers in Type Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors Reviewed

    Inaba Hidefumi, Kaido Yosuke, Ito Saya, Hirobata Tomonao, Inoue Gen, Sugita Takakazu, Yamamoto Yuki, Jinnin Masatoshi, Kimura Hiroaki, Kobayashi Tomoko, Iwama Shintaro, Arima Hiroshi, Matsuoka Takaaki

    ENDOCRINOLOGY AND METABOLISM   Vol. 37 ( 1 ) page: 84 - +   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Endocrinology and Metabolism  

    Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P= 0.022; 11/14 vs. 7/26, P= 0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion: Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

    DOI: 10.3803/EnM.2021.1282

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  6. Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults. Reply to Sugiyama K and Saisho Y [letter]

    Wada Eri, Onoue Takeshi, Kinoshita Tamaki, Hayase Ayaka, Handa Tomoko, Ito Masaaki, Furukawa Mariko, Okuji Takayuki, Kobayashi Tomoko, Iwama Shintaro, Sugiyama Mariko, Takagi Hiroshi, Hagiwara Daisuke, Suga Hidetaka, Banno Ryoichi, Goto Motomitsu, Arima Hiroshi

    DIABETOLOGIA   Vol. 65 ( 1 ) page: 252 - 253   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Diabetologia  

    DOI: 10.1007/s00125-021-05610-4

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  7. Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice Reviewed

    Yaginuma H., Banno R., Sun R., Taki K., Mizoguchi A., Kobayashi T., Sugiyama M., Tsunekawa T., Onoue T., Takagi H., Hagiwara D., Ito Y., Iwama S., Suga H., Arima H.

    Journal of Pharmacological Sciences   Vol. 147 ( 4 ) page: 340 - 347   2021.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Pharmacological Sciences  

    We investigated whether peripheral combination treatment of a sodium–glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptozotocin to produce IDDM. IDDM mice were then divided into five groups: SGLT2 inhibitor treatment alone, leptin treatment alone, leptin and SGLT2 inhibitor co-treatment, untreated IDDM mice, and healthy mice groups. The blood glucose (BG) level at the end of the dark cycle was measured, and a glucose tolerance test (GTT) was performed and compared between the five groups. Leptin was peripherally administered at 20 μg/day using an osmotic pump, and an SGLT2 inhibitor, ipragliflozin, was orally administered at 3 mg/kg/day. Monotherapy with SGLT2 inhibitor or leptin significantly improved glucose metabolism in mice as evaluated by BG and GTT compared with the untreated group, whereas the co-treatment group with SGLT2 inhibitor and leptin further improved glucose metabolism as compared with the monotherapy group. Notably, glucose metabolism in the co-treatment group improved to the same level as that in the healthy mice group. Thus, peripheral combination treatment with leptin and SGLT2 inhibitor improved glucose metabolism in IDDM mice without the use of insulin.

    DOI: 10.1016/j.jphs.2021.08.010

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  8. Adult-onset autoimmune diabetes identified by glutamic acid decarboxylase autoantibodies: a retrospective cohort study Reviewed

    Wada Eri, Onoue Takeshi, Kinoshita Tamaki, Hayase Ayaka, Handa Tomoko, Ito Masaaki, Furukawa Mariko, Okuji Takayuki, Kobayashi Tomoko, Iwama Shintaro, Sugiyama Mariko, Takagi Hiroshi, Hagiwara Daisuke, Suga Hidetaka, Banno Ryoichi, Goto Motomitsu, Arima Hiroshi

    DIABETOLOGIA   Vol. 64 ( 10 ) page: 2183 - 2192   2021.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Diabetologia  

    Aims/hypothesis: Patients with GAD antibodies (GADAb) showing clinical features of type 2 diabetes typically exhibit progression to an insulin-dependent state in several months or years. This condition is diagnosed as slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults, a subtype of adult-onset autoimmune diabetes. However, some patients diagnosed with adult-onset autoimmune diabetes do not progress to an insulin-dependent state. We conducted a retrospective cohort study to identify patients with non-insulin-dependent diabetes among those diagnosed with adult-onset autoimmune diabetes using measurable indicators in routine clinical practice. Methods: We surveyed data from the electronic medical records of all patients with GADAb from eight medical centres in Japan for selecting and analysing patients who matched the diagnostic criteria of SPIDDM. Results: Overall, 345 patients were analysed; of these, 162 initiated insulin therapy (insulin therapy group), whereas 183 did not (non-insulin therapy group) during the follow-up period (median 3.0 years). Patients in the non-insulin therapy group were more likely to be male and presented a later diabetes onset, shorter duration of diabetes, higher BMI, higher blood pressure levels, lower HbA1c levels, lower GADAb levels and lesser antidiabetic agent use than those in the insulin therapy group when GADAb was first identified as positive. A Cox proportional hazards model showed that BMI, HbA1c levels and GADAb levels were independent factors for progression to insulin therapy. Kaplan–Meier analyses revealed that 86.0% of the patients with diabetes having GADAb who presented all three factors (BMI ≥ 22 kg/m2, HbA1c < 75 mmol/mol [9.0%] and GADAb <10.0 U/ml) did not require insulin therapy for 4 years. Conclusions/interpretation: Higher BMI (≥22 kg/m2), lower HbA1c (<75 mmol/mol [9.0%]) and lower GADAb levels (<10.0 U/ml) can predict a non-insulin-dependent state for at least several years in Japanese patients with diabetes having GADAb. Graphical abstract: [Figure not available: see fulltext.]

    DOI: 10.1007/s00125-021-05516-1

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  9. GABA(B) receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice Reviewed International coauthorship

    Sun Runan, Tsunekawa Taku, Hirose Tomonori, Yaginuma Hiroshi, Taki Keigo, Mizoguchi Akira, Miyata Takashi, Kobayashi Tomoko, Sugiyama Mariko, Onoue Takeshi, Takagi Hiroshi, Hagiwara Daisuke, Ito Yoshihiro, Iwama Shintaro, Suga Hidetaka, Banno Ryoichi, Bettler Bernhard, Arima Hiroshi

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 19296   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Scientific Reports  

    Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.

    DOI: 10.1038/s41598-021-98590-9

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  10. Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice. Reviewed

    Mizoguchi A, Banno R, Sun R, Yaginuma H, Taki K, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Nagai T, Yamada K, Arima H

    Scientific reports   Vol. 11 ( 1 ) page: 12873   2021.6

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    The reward system, which consists of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens and caudate-putamen in the striatum, has an important role in the pathogenesis of not only drug addiction but also diet-induced obesity. In the present study, we examined whether signaling through glucocorticoid receptors (GRs) in the reward system affects the rewarding value of a high-fat diet (HFD). To do so, we generated mice that lack functional GRs specifically in dopaminergic neurons (D-KO mice) or corticostriatal neurons (CS-KO mice), subjected the mice to caloric restriction stress conditions, and evaluated the rewarding value of a HFD by conditioned place preference (CPP) test. Caloric restriction induced increases in serum corticosterone to similar levels in all genotypes. While CS-KO as well as WT mice exhibited a significant preference for HFD in the CPP test, D-KO mice exhibited no such preference. There were no differences between WT and D-KO mice in consumption of HFD after fasting or cognitive function evaluated by a novel object recognition test. These data suggest that glucocorticoid signaling in the VTA increases the rewarding value of a HFD under restricted caloric stress.

    DOI: 10.1038/s41598-021-92386-7

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  11. CD4<sup>+</sup> T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice. Reviewed

    Yasuda Y, Iwama S, Sugiyama D, Okuji T, Kobayashi T, Ito M, Okada N, Enomoto A, Ito S, Yan Y, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Goto M, Suga H, Banno R, Takahashi M, Nishikawa H, Arima H

    Science translational medicine   Vol. 13 ( 593 )   2021.5

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Science translational medicine  

    DOI: 10.1126/scitranslmed.abb7495

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  12. High-fat Feeding Causes Inflammation and Insulin Resistance in the Ventral Tegmental Area in Mice. Reviewed

    Mizoguchi A, Banno R, Sun R, Yaginuma H, Taki K, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Arima H

    Neuroscience   Vol. 461   page: 72 - 79   2021.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Neuroscience  

    DOI: 10.1016/j.neuroscience.2021.02.009

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  13. Arginine vasopressin-Venus reporter mice as a tool for studying magnocellular arginine vasopressin neurons Reviewed

    Hagiwara Daisuke, Tochiya Masayoshi, Azuma Yoshinori, Tsumura Tetsuro, Hodai Yuichi, Kawaguchi Yohei, Miyata Takashi, Kobayashi Tomoko, Sugiyama Mariko, Onoue Takeshi, Takagi Hiroshi, Ito Yoshihiro, Iwama Shintaro, Suga Hidetaka, Banno Ryoichi, Arima Hiroshi

    PEPTIDES   Vol. 139   page: 170517   2021.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Peptides  

    DOI: 10.1016/j.peptides.2021.170517

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  14. Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors. Reviewed

    Kobayashi T, Iwama S, Sugiyama D, Yasuda Y, Okuji T, Ito M, Ito S, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Nishikawa H, Arima H

    Journal for immunotherapy of cancer   Vol. 9 ( 5 )   2021.5

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1136/jitc-2021-002493

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  15. Efficacies of programmed cell death 1 ligand 1 blockade in non-small cell lung cancer patients with acquired resistance to prior programmed cell death 1 inhibitor and development of diabetic ketoacidosis caused by two different etiologies: a retrospective case series. Reviewed

    Ishi A, Tanaka I, Iwama S, Sakakibara T, Mastui T, Kobayashi T, Hase T, Morise M, Sato M, Arima H, Hashimoto N

    Endocrine journal   Vol. 68 ( 5 ) page: 613 - 620   2021.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本内分泌学会  

    <p>The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis is vital for immune resistance during tumor development, while PD-L1 inhibitors can also inhibit the PD-L1/B7-1 (CD80) interaction, indicating one of the molecular differences between PD-1 and PD-L1 inhibitors. However, the clinical benefits of PD-L1 inhibitors in patients previously treated with PD-1 inhibitors remain unknown. In this study, we retrospectively analyzed the clinical data of eight patients with non-small cell lung cancer who received the PD-L1 inhibitor atezolizumab and previously treated with the PD-1 inhibitor nivolumab. The median progression-free survival was 2.1 months (1.8–18.7 months), and 4 of 8 patients achieved at least stable disease. In two of these patients, atezolizumab treatment resulted in longer progression-free survival (PFS) compared with that of nivolumab. Conversely, one patient exhibited grade 4 diabetic ketoacidosis (DKA) within 2 weeks after the initial administration of atezolizumab. Another patient had developed type 1 diabetes mellitus (T1DM) during the prior nivolumab treatment and then developed DKA due to an infection after the initiation of atezolizumab. Both of them had high-risk human leukocyte antigen-DR/DQ types relevant to T1DM. These results demonstrate the potential efficacy of PD-L1 inhibitors to some tumors that have acquired resistance to PD-1 inhibitors and suggest that appropriate managements are required for not only a newly onset of T1DM but also blood glucose control after the development of T1DM during a reiteration of the PD-1/PD-L1 blockade.</p>

    DOI: 10.1507/endocrj.EJ20-0769

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  16. Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors. Invited Reviewed

    Iwama S, Kobayashi T, Arima H

    Endocrinology and metabolism (Seoul, Korea)   Vol. 36 ( 2 ) page: 312 - 321   2021.4

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Endocrinology and Metabolism  

    DOI: 10.3803/EnM.2021.1007

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  17. Dietary sodium chloride attenuates increased beta-cell mass to cause glucose intolerance in mice under a high-fat diet Reviewed

    Taki Keigo, Takagi Hiroshi, Hirose Tomonori, Sun Runan, Yaginuma Hiroshi, Mizoguchi Akira, Kobayashi Tomoko, Sugiyama Mariko, Tsunekawa Taku, Onoue Takeshi, Hagiwara Daisuke, Ito Yoshihiro, Iwama Shintaro, Suga Hidetaka, Banno Ryoichi, Sakano Daisuke, Kume Shoen, Arima Hiroshi

    PLOS ONE   Vol. 16 ( 3 ) page: e0248065   2021.3

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  18. Deficiency of WFS1 leads to the impairment of AVP secretion under dehydration in male mice Reviewed

    Kurimoto Junki, Takagi Hiroshi, Miyata Takashi, Hodai Yuichi, Kawaguchi Yohei, Hagiwara Daisuke, Suga Hidetaka, Kobayashi Tomoko, Sugiyama Mariko, Onoue Takeshi, Ito Yoshihiro, Iwama Shintaro, Banno Ryoichi, Tanabe Katsuya, Tanizawa Yukio, Arima Hiroshi

    PITUITARY     2021.3

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    DOI: 10.1007/s11102-021-01135-6

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  19. Anti-pituitary antibodies as a marker of autoimmunity in pituitary glands. Invited Reviewed

    Iwama S, Arima H

    Endocrine journal   Vol. 67 ( 11 ) page: 1077 - 1083   2020.11

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    DOI: 10.1507/endocrj.EJ20-0436

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  20. Endoplasmic reticulum chaperone BiP/GRP78 knockdown leads to autophagy and cell death of arginine vasopressin neurons in mice Reviewed

    Kawaguchi Yohei, Hagiwara Daisuke, Miyata Takashi, Hodai Yuichi, Kurimoto Junki, Takagi Hiroshi, Suga Hidetaka, Kobayashi Tomoko, Sugiyama Mariko, Onoue Takeshi, Ito Yoshihiro, Iwama Shintaro, Banno Ryoichi, Grinevich Valery, Arima Hiroshi

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 19730   2020.11

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    DOI: 10.1038/s41598-020-76839-z

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  21. Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons

    Miyata Takashi, Hagiwara Daisuke, Hodai Yuichi, Miwata Tsutomu, Kawaguchi Yohei, Kurimoto Junki, Ozaki Hajime, Mitsumoto Kazuki, Takagi Hiroshi, Suga Hidetaka, Kobayashi Tomoko, Sugiyama Mariko, Onoue Takeshi, Ito Yoshihiro, Iwama Shintaro, Banno Ryoichi, Matsumoto Mami, Kawakami Natsuko, Ohno Nobuhiko, Sakamoto Hirotaka, Arima Hiroshi

    ISCIENCE   Vol. 23 ( 10 ) page: 101648   2020.10

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    DOI: 10.1016/j.isci.2020.101648

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  22. Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial

    Wada E.

    BMJ open diabetes research &amp; care   Vol. 8 ( 1 )   2020.6

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    DOI: 10.1136/bmjdrc-2019-001115

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  23. Hypothalamic glial cells isolated by MACS reveal that microglia and astrocytes induce hypothalamic inflammation via different processes under high-fat diet conditions Reviewed International journal

    Mariko Sugiyama, Ryoichi Banno, Hiroshi Yaginuma, Keigo Taki, Akira Mizoguchi, Taku Tsunekawa, Takeshi Onoue, Hiroshi Takagi, Yoshihiro Ito, Shintaro Iwama, Motomitsu Goto, Hidetaka Suga, Okiru Komine, Koji Yamanaka, Hiroshi Arima

    Neurochemistry International   Vol. 136   page: 104733 - 104733   2020.6

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    DOI: 10.1016/j.neuint.2020.104733

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  24. Diagnosis and treatment of autoimmune and IgG4-related hypophysitis: clinical guidelines of the Japan Endocrine Society. Reviewed

    Takagi H, Iwama S, Sugimura Y, Takahashi Y, Oki Y, Akamizu T, Arima H

    Endocrine journal     2020.2

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    DOI: 10.1507/endocrj.EJ19-0569

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  25. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Reviewed

    Okada N, Iwama S, Okuji T, Kobayashi T, Yasuda Y, Wada E, Onoue T, Goto M, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Hase T, Morise M, Kanda M, Yokota K, Hashimoto N, Ando M, Fujimoto Y, Nagino M, Kodera Y, Fujishiro M, Hibi H, Sone M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H

    British journal of cancer     2020.2

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    DOI: 10.1038/s41416-020-0736-7

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  26. [Endocrine Dysfunction Associated with Immune Checkpoint Blockade].

    Iwama S

    Gan to kagaku ryoho. Cancer & chemotherapy   Vol. 47 ( 2 ) page: 203-206   2020.2

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  27. Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells Reviewed International journal

    Kasai Takatoshi, Suga Hidetaka, Sakakibara Mayu, Ozone Chikafumi, Matsumoto Ryusaku, Kano Mayuko, Mitsumoto Kazuki, Ogawa Koichiro, Kodani Yu, Nagasaki Hiroshi, Inoshita Naoko, Sugiyama Mariko, Onoue Takeshi, Tsunekawa Taku, Ito Yoshihiro, Takagi Hiroshi, Hagiwara Daisuke, Iwama Shintaro, Goto Motomitsu, Banno Ryoichi, Takahashi Jun, Arima Hiroshi

    CELL REPORTS   Vol. 30 ( 1 ) page: 18 - +   2020.1

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    DOI: 10.1016/j.celrep.2019.12.009

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  28. Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study. Reviewed International journal

    Tomoko Kobayashi, Shintaro Iwama, Yoshinori Yasuda, Norio Okada, Takayuki Okuji, Masaaki Ito, Takeshi Onoue, Motomitsu Goto, Mariko Sugiyama, Taku Tsunekawa, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Ryoichi Banno, Kenji Yokota, Tetsunari Hase, Masahiro Morise, Naozumi Hashimoto, Masahiko Ando, Yasushi Fujimoto, Hideharu Hibi, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Yoshinori Hasegawa, Hiroshi Arima

    Journal for immunotherapy of cancer   Vol. 8 ( 2 )   2020

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    BACKGROUND: Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM). METHODS: A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint. RESULTS: Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05). CONCLUSIONS: In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone. CLINICAL TRIALS REGISTRATION: UMIN000019024.

    DOI: 10.1136/jitc-2020-000779

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  29. Anti-pituitary antibodies as a marker of autoimmunity in pituitary glands International journal

    Iwama Shintaro, Arima Hiroshi

    ENDOCRINE JOURNAL   Vol. 67 ( 11 ) page: 1077 - 1083   2020

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  30. Dipeptidyl peptidase-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels in patients with type 2 diabetes: A randomized controlled trial.

    Onoue T, Goto M, Wada E, Furukawa M, Okuji T, Okada N, Kobayashi T, Iwama S, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Seino Y, Suga H, Banno R, Hamada Y, Ando M, Yamamori E, Arima H

    PloS one   Vol. 15 ( 1 ) page: e0228004   2020

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  31. Diagnosis of central diabetes insipidus using a vasopressin radioimmunoassay during hypertonic saline infusion.

    Takagi H, Hagiwara D, Handa T, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Iwama S, Goto M, Suga H, Banno R, Takahashi K, Matsui S, Arima H

    Endocrine journal     2019.11

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    DOI: 10.1507/endocrj.EJ19-0224

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  32. GABA<sub>B</sub> Receptor Signaling in the Mesolimbic System Suppresses Binge-like Consumption of a High-Fat Diet.

    Tsunekawa T, Banno R, Yaginuma H, Taki K, Mizoguchi A, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Bettler B, Arima H

    iScience   Vol. 20   page: 337-347   2019.10

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    DOI: 10.1016/j.isci.2019.09.032

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  33. Improved methods for the differentiation of hypothalamic vasopressin neurons using mouse induced pluripotent stem cells. International journal

    Mitsumoto K, Suga H, Sakakibara M, Soen M, Yamada T, Ozaki H, Nagai T, Kano M, Kasai T, Ozone C, Ogawa K, Sugiyama M, Onoue T, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Banno R, Arima H

    Stem cell research   Vol. 40   page: 101572   2019.10

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    DOI: 10.1016/j.scr.2019.101572

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  34. Severe hypocalcemia following denosumab treatment in a patient with secondary osteoporosis associated with primary sclerosing cholangitis.

    Yasuda Y, Iwama S, Arima H

    Endocrine journal   Vol. 66 ( 3 ) page: 271-275   2019.3

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    DOI: 10.1507/endocrj.EJ18-0545

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  35. Effect of prior chronic aerobic exercise on overload-induced skeletal muscle hypertrophy in mice.

    Siriguleng S, Koike T, Natsume Y, Iwama S, Oshida Y

    Physiological research   Vol. 67 ( 5 ) page: 765-775   2018.11

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  36. Effect of prior chronic aerobic exercise on overload-induced skeletal muscle hypertrophy in mice.

    Siriguleng S, Koike T, Natsume Y, Iwama S, Oshida Y

    Physiological research   Vol. 67 ( 5 ) page: 765-775   2018.11

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  37. Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab. Reviewed

    Kimbara S, Fujiwara Y, Iwama S, Ohashi K, Kuchiba A, Arima H, Yamazaki N, Kitano S, Yamamoto N, Ohe Y

    Cancer science   Vol. 109 ( 11 ) page: 3583-3590   2018.11

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    DOI: 10.1111/cas.13800

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  38. Chemical chaperone 4-phenylbutylate reduces mutant protein accumulation in the endoplasmic reticulum of arginine vasopressin neurons in a mouse model for familial neurohypophysial diabetes insipidus. Reviewed

    Tochiya M, Hagiwara D, Azuma Y, Miyata T, Morishita Y, Suga H, Onoue T, Tsunekawa T, Takagi H, Ito Y, Iwama S, Goto M, Banno R, Arima H

    Neuroscience letters   Vol. 682   page: 50-55   2018.6

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    DOI: 10.1016/j.neulet.2018.06.013

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  39. Association of pre-existing thyroid autoimmunity with the development of thyroid dysfunction induced by nivolumab.

    Kimbara Shiro, Fujiwara Yutaka, Iwama Shintaro, Ohashi Ken, Kuchiba Aya, Arima Hiroshi, Yamazaki Naoya, Kitano Shigehisa, Yamamoto Noboru, Ohe Yuichiro

    JOURNAL OF CLINICAL ONCOLOGY   Vol. 36 ( 15 ) page: .   2018.5

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  40. Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis. Reviewed

    Yasuda Y, Iwama S, Kiyota A, Izumida H, Nakashima K, Iwata N, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Enomoto A, Takahashi M, Arima H, Sugimura Y

    The Journal of pathology   Vol. 244 ( 4 ) page: 469-478   2018.4

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    DOI: 10.1002/path.5046

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  41. Cullin-associated NEDD8-dissociated protein 1, a novel interactor of rabphilin-3A, deubiquitylates rabphilin-3A and regulates arginine vasopressin secretion in PC12 cells. Reviewed

    Nakashima K, Takeuchi S, Iwama S, Kiyota A, Yasuda Y, Iwata N, Enomoto A, Arima H, Sugimura Y

    Endocrine journal   Vol. 65 ( 3 ) page: 325-334   2018.3

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    DOI: 10.1507/endocrj.EJ17-0399

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  42. Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. Reviewed

    Kobayashi T, Iwama S, Yasuda Y, Okada N, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Yokota K, Hase T, Morise M, Hashimoto N, Ando M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H

    Journal of the Endocrine Society   Vol. 2 ( 3 ) page: 241-251   2018.3

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    DOI: 10.1210/js.2017-00432

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  43. Sequestosome 1 (SQSTMI/p62) maintains protein folding capacity under endoplasmic reticulum stress in mouse hypothalamic organotypic culture Reviewed

    Tominaga Takashi, Goto Motomitsu, Onoue Takeshi, Mizoguchi Akira, Sugiyama Mariko, Tsunekawa Taku, Hagiwara Daisuke, Morishita Yoshiaki, Ito Yoshihiro, Iwama Shintaro, Suga Hidetaka, Banno Ryoichi, Arima Hiroshi

    NEUROSCIENCE LETTERS   Vol. 656   page: 103-107   2017.8

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    DOI: 10.1016/j.neulet.2017.06.014

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  44. PTP1B deficiency improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under high-fat diet conditions. Reviewed

    Sugiyama M, Banno R, Mizoguchi A, Tominaga T, Tsunekawa T, Onoue T, Hagiwara D, Ito Y, Morishita Y, Iwama S, Goto M, Suga H, Arima H

    Biochemical and biophysical research communications   Vol. 488 ( 1 ) page: 116-121   2017.6

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    DOI: 10.1016/j.bbrc.2017.05.019

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  45. Deficiency of PTP1B Attenuates Hypothalamic Inflammation Via Activation of the JAK2-STAT3 Pathway in Microglia. Reviewed

    Tsunekawa T, Banno R, Mizoguchi A, Sugiyama M, Tominaga T, Onoue T, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Sugimura Y, Arima H

    EBioMedicine     2017.1

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    DOI: 10.1016/j.ebiom.2017.01.007

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  46. WS1-3 免疫チェックポイント阻害薬による下垂体障害・下垂体炎

    岩間 信太郎, 有馬 寛

    日本臨床免疫学会会誌   Vol. 40 ( 4 ) page: 264a-264a   2017

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    <p>  免疫チェックポイント阻害薬で認められる免疫関連有害事象(immune-related adverse events; irAEs)は全身の臓器で認められ,大腸炎,肝炎,間質性肺炎,皮膚炎,神経・筋障害,内分泌障害などが報告されている.死亡に至る重篤例もあることから適切な対応が重要である.irAEsとして障害される内分泌器官は下垂体,甲状腺,副腎皮質,膵,副甲状腺が挙げられ,それぞれ異なる対応を要する.下垂体障害の頻度は細胞傷害性T細胞抗原(cytotoxic T-lymphocyte-associated antigen; CTLA)-4に対する抗体であるイピリムマブで4-10%程度,programmed cell death(PD)-1に対する抗体で1%未満と報告されている.下垂体前葉機能障害および下垂体腫大を呈する症例は臨床的に下垂体炎と考えられる.内分泌学的には副腎皮質刺激ホルモン(ACTH)の障害が最も高頻度で認められ,診断が遅れると副腎クリーゼとなり得る重篤な副作用である.これまでに報告された抗PD-1抗体または抗CTLA-4抗体による下垂体障害・下垂体炎の症例を検討した結果,両者の臨床的特徴には相違点があることが解ってきた.本講演では,抗PD-1抗体または抗CTLA-4抗体による下垂体障害・下垂体炎について臨床的特徴をそれぞれ解説し,両者の相違点について考察する.</p>

    DOI: 10.2177/jsci.40.264a

  47. Normalization of Bilateral Adrenal Gland Enlargement after Treatment for Cryptococcosis. Reviewed

    Muraoka Y, Iwama S, Arima H

    Case reports in endocrinology   Vol. 2017   page: 1543149   2017

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  48. Clinical practice and mechanism of endocrinological adverse events associated with immune checkpoint inhibitors.

    Iwama S, Arima H

    Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology   Vol. 40 ( 2 ) page: 90-94   2017

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  49. Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. Reviewed

    Iwata N, Iwama S, Sugimura Y, Yasuda Y, Nakashima K, Takeuchi S, Hagiwara D, Ito Y, Suga H, Goto M, Banno R, Caturegli P, Koike T, Oshida Y, Arima H

    Pituitary     2016.11

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    DOI: 10.1007/s11102-016-0780-8

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  50. Tomosyn Negatively Regulates Arginine Vasopressin Secretion in Embryonic Stem Cell-Derived Neurons. Reviewed

    Takeuchi S, Iwama S, Takagi H, Kiyota A, Nakashima K, Izumida H, Fujisawa H, Iwata N, Suga H, Watanabe T, Kaibuchi K, Oiso Y, Arima H, Sugimura Y

    PloS one   Vol. 11 ( 10 ) page: e0164544   2016.10

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  51. NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats. Reviewed

    Izumida H, Takagi H, Fujisawa H, Iwata N, Nakashima K, Takeuchi S, Iwama S, Namba T, Komatu Y, Kaibuchi K, Oiso Y, Arima H, Sugimura Y

    Experimental neurology     2016.8

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    DOI: 10.1016/j.expneurol.2016.08.007

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  52. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

    Fujisawa Haruki, Sugimura Yoshihisa, Takagi Hiroshi, Mizoguchi Hiroyuki, Takeuchi Hideyuki, Izumida Hisakazu, Nakashima Kohtaro, Ochiai Hiroshi, Takeuchi Seiji, Kiyota Atsushi, Fukumoto Kazuya, Iwama Shintaro, Takagishi Yoshiko, Hayashi Yoshitaka, Arima Hiroshi, Komatsu Yukio, Murata Yoshiharu, Oiso Yutaka

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   Vol. 27 ( 3 ) page: 766-780   2016.3

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  53. WS2-4 免疫チェックポイント阻害剤による内分泌副作用の臨床とそのメカニズム

    岩間 信太郎, 有馬 寛

    日本臨床免疫学会会誌   Vol. 39 ( 4 ) page: 350b-350b   2016

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    <p>  免疫チェックポイント阻害剤はT細胞の活性化を負に制御する分子に対するモノクローナル抗体で,細胞傷害性T細胞抗原(CTLA)4に対する抗体であるイピリムマブ(Ipi)とprogrammed cell death-1に対する抗体であるニボルマブが本邦でも近年使用開始された.これらの薬剤は,優れた抗腫瘍効果の一方で,自己免疫機序が想定される重篤な副作用を発症させ,特に,肝炎,腸炎,皮膚炎,内分泌障害が好発する.内分泌副作用として,下垂体炎,甲状腺機能異常症,副腎炎,1型糖尿病などが報告されており,薬剤によりその発症頻度は異なる.特に我々は,従来まれな疾患と考えられてきた下垂体炎が,Ipi使用者において約10%もの頻度で発症することに着目し,抗マウスCTLA4抗体をSJLマウスに連続投与することで下垂体に炎症細胞浸潤を呈する抗CTLA4抗体誘発下垂体炎マウスモデルを作成した.本マウスにおける病態解析を進め,抗CTLA4抗体は下垂体に発現するCTLA4に直接結合し,補体活性化を介したII型アレルギー反応により下垂体に炎症を誘発する可能性を報告した.さらに,Ipiにより下垂体炎を発症した患者血清中に抗下垂体抗体が存在することを明らかにし,臨床における抗下垂体抗体の診断的有用性を示した.本講演では抗CTLA4抗体による下垂体炎の発症メカニズムおよび実際の症例を紹介するとともに,現在名古屋大学で行っている臨床研究についても紹介したい.</p>

    DOI: 10.2177/jsci.39.350b

  54. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments. Reviewed

    Fujisawa H, Sugimura Y, Takagi H, Mizoguchi H, Takeuchi H, Izumida H, Nakashima K, Ochiai H, Takeuchi S, Kiyota A, Fukumoto K, Iwama S, Takagishi Y, Hayashi Y, Arima H, Komatsu Y, Murata Y, Oiso Y

    Journal of the American Society of Nephrology : JASN     2015.9

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    DOI: 10.1681/ASN.2014121196

    PubMed

  55. Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. Reviewed

    Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y

    The Journal of clinical endocrinology and metabolism   Vol. 100 ( 7 ) page: E946-54   2015.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/jc.2014-4209

    PubMed

  56. Identification of the novel autoantigen candidate Rab GDP dissociation inhibitor alpha in isolated adrenocorticotropin deficiency

    Kiyota Atsushi, Iwama Shintaro, Sugimura Yoshihisa, Takeuchi Seiji, Takagi Hiroshi, Iwata Naoko, Nakashima Kohtaro, Suzuki Haruyuki, Nishioka Tomoki, Kato Takuya, Enomoto Atsushi, Arima Hiroshi, Kaibuchi Kozo, Oiso Yutaka

    ENDOCRINE JOURNAL   Vol. 62 ( 2 ) page: 153-160   2015.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    Web of Science

  57. Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival. Reviewed

    De Remigis A, de Gruijl TD, Uram JN, Tzou SC, Iwama S, Talor MV, Armstrong TD, Santegoets SJ, Slovin SF, Zheng L, Laheru DA, Jaffee EM, Gerritsen WR, van den Eertwegh AJ, Le DT, Caturegli P

    International journal of cancer. Journal international du cancer   Vol. 136 ( 1 ) page: 127-37   2015.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ijc.28973

    PubMed

  58. Identification of the novel autoantigen candidate Rab GDP dissociation inhibitor alpha in isolated adrenocorticotropin deficiency. Reviewed

    Kiyota A, Iwama S, Sugimura Y, Takeuchi S, Takagi H, Iwata N, Nakashima K, Suzuki H, Nishioka T, Kato T, Enomoto A, Arima H, Kaibuchi K, Oiso Y

    Endocrine journal   Vol. 62 ( 2 ) page: 153-60   2015

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1507/endocrj.EJ14-0369

    PubMed

  59. Minocycline prevents osmotic demyelination associated with aquaresis. Reviewed

    Takagi H, Sugimura Y, Suzuki H, Iwama S, Izumida H, Fujisawa H, Ogawa K, Nakashima K, Ochiai H, Takeuchi S, Kiyota A, Suga H, Goto M, Banno R, Arima H, Oiso Y

    Kidney international   Vol. 86 ( 5 ) page: 954-64   2014.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ki.2014.119

    PubMed

  60. Detection of pituitary antibodies by immunofluorescence: approach and results in patients with pituitary diseases. Reviewed

    Ricciuti A, De Remigis A, Landek-Salgado MA, De Vincentiis L, Guaraldi F, Lupi I, Iwama S, Wand GS, Salvatori R, Caturegli P

    The Journal of clinical endocrinology and metabolism   Vol. 99 ( 5 ) page: 1758-66   2014.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/jc.2014-1049

    PubMed

  61. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Reviewed

    Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P

    Science translational medicine   Vol. 6 ( 230 ) page: 230ra45   2014.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/scitranslmed.3008002

    PubMed

  62. Isolated prolactin deficiency associated with serum autoantibodies against prolactin-secreting cells. Reviewed

    Iwama S, Welt CK, Romero CJ, Radovick S, Caturegli P

    The Journal of clinical endocrinology and metabolism   Vol. 98 ( 10 ) page: 3920-5   2013.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/jc.2013-2411

    PubMed

  63. From Japan with love: another tessera in the hypophysitis mosaic. Reviewed

    Caturegli P, Iwama S

    The Journal of clinical endocrinology and metabolism   Vol. 98 ( 5 ) page: 1865-8   2013.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/jc.2013-1912

    PubMed

  64. Hashimoto's thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. Reviewed

    Caturegli P, De Remigis A, Chuang K, Dembele M, Iwama A, Iwama S

    Thyroid : official journal of the American Thyroid Association   Vol. 23 ( 2 ) page: 142-50   2013.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1089/thy.2012.0554

    PubMed

  65. Anatabine ameliorates experimental autoimmune thyroiditis. Reviewed

    Caturegli P, De Remigis A, Ferlito M, Landek-Salgado MA, Iwama S, Tzou SC, Ladenson PW

    Endocrinology   Vol. 153 ( 9 ) page: 4580-7   2012.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/en.2012-1452

    PubMed

  66. Hürthle cells predict hypothyroidism in interferon-γ transgenic mice of different genetic backgrounds. Reviewed

      Vol. 153 ( 8 ) page: 4059-66   2012.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1210/en.2012-1236

    PubMed

  67. Assessment of long-term efficacy and safety of metyrapone monotherapy in a patient with ACTH-independent macronodular adrenal hyperplasia. Reviewed

    Yoshida M, Umeda H, Iwama S, Nakayama S, Miyata M, Ogawa K, Maeda H, Oiso Y

    Endocrine   Vol. 41 ( 1 ) page: 160-1   2012.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s12020-011-9549-z

    PubMed

  68. Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome. Reviewed

    Iwama S, Sugimura Y, Suzuki H, Suzuki H, Murase T, Ozaki N, Nagasaki H, Arima H, Murata Y, Sawada M, Oiso Y

    Glia   Vol. 59 ( 3 ) page: 452-62   2011.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/glia.21114

    PubMed

  69. Minocycline prevents osmotic demyelination syndrome by inhibiting the activation of microglia.

    Suzuki H, Sugimura Y, Iwama S, Suzuki H, Nobuaki O, Nagasaki H, Arima H, Sawada M, Oiso Y

    Journal of the American Society of Nephrology : JASN   Vol. 21 ( 12 ) page: 2090-8   2010.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1681/ASN.2010040438

    PubMed

  70. Central adiponectin functions to inhibit arginine vasopressin release in conscious rats. Reviewed

    Iwama S, Sugimura Y, Murase T, Hiroi M, Goto M, Hayashi M, Arima H, Oiso Y

    Journal of neuroendocrinology   Vol. 21 ( 9 ) page: 753-9   2009.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1365-2826.2009.01894.x

    PubMed

  71. Acute suppurative thyroiditis extending to descending necrotizing mediastinitis and pericarditis.

    Iwama S, Kato Y, Nakayama S

    Thyroid : official journal of the American Thyroid Association   Vol. 17 ( 3 ) page: 281-2   2007.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1089/thy.2006.0121

    PubMed

▼display all

Books 63

  1. 糖尿病・内分泌代謝科/自己免疫性視床下部下垂体炎および関連疾患の病因と病態

    岩間信太郎( Role: Sole author)

    科学評論社  2021.12 

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    Responsible for pages:687-692   Language:Japanese Book type:Textbook, survey, introduction

  2. 下垂体疾患診療マニュアル改訂第3版/中枢性尿崩症

    岩間信太郎、有馬寛( Role: Joint author)

    診断と治療社  2021.12 

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    Responsible for pages:260-264   Language:Japanese Book type:Textbook, survey, introduction

  3. Medical Practice/免疫チェックポイント阻害薬による副作用を事前に予測する

    岩間信太郎( Role: Joint author)

    文光堂  2021.11 

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    Responsible for pages:38(11), p1753   Language:Japanese

  4. 日本医事新報/私の治療/免疫チェックポイント阻害薬による内分泌代謝異常

    岩間信太郎、有馬寛

    日本醫事新報社  2021.10 

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    Responsible for pages:10月4週号 p45-46   Language:Japanese Book type:Textbook, survey, introduction

  5. 日本医師会雑誌 内分泌疾患・糖尿病・代謝疾患―診療のエッセンス/免疫チェックポイント阻害薬の副作用としての内分泌疾患

    岩間信太郎、有馬寛( Role: Joint author)

    日本医師会  2021.10 

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    Responsible for pages:第150巻・特別号(2), S144-S148   Language:Japanese

  6. 最新ガイドラインに基づく代謝・内分泌疾患 診療指針 2021-’22/免疫チェックポイント阻害薬治療に関連した内分泌疾患

    岩間信太郎、有馬寛( Role: Joint author)

    総合医学社  2021.9  ( ISBN:9784883787388

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    Total pages:520   Responsible for pages:487-494   Language:Japanese Book type:Textbook, survey, introduction

  7. 医療/免疫チェックポイント阻害薬による有害事象:知っておくべき内分泌障害 Reviewed

    岩間信太郎( Role: Joint author)

    国立医療学会  2021.8 

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    Responsible for pages:75(4), p336-339   Language:Japanese

  8. 臨床検査/電解質異常をきたす内分泌疾患 ナトリウム異常と内分泌疾患

    岩間信太郎( Role: Joint author)

    医学書院  2021.8 

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    Responsible for pages:65(8):798-804   Language:Japanese Book type:Textbook, survey, introduction

  9. 日本臨牀「皮膚悪性腫瘍(第2版)上」/irAEの治療-下垂体機能低下症

    岩間信太郎( Role: Joint author)

    日本臨床社  2021.5 

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    Total pages:517   Responsible for pages:427-430   Language:Japanese Book type:Textbook, survey, introduction

  10. 医学のあゆみ/下垂体の免疫関連有害事象

    岩間信太郎、有馬寛( Role: Joint author)

    医歯薬出版株式会社  2021.2 

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    Responsible for pages:276(8), 782-785   Language:Japanese Book type:Scholarly book

  11. お医者さんオンライン/尿崩症

    岩間信太郎、有馬寛( Role: Joint author)

    有限会社エイド出版  2020.11 

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    Language:Japanese Book type:Textbook, survey, introduction

  12. 免疫チェックポイント阻害薬実践ガイドブック

    岩間信太郎( Role: Joint author ,  下垂体機能障害(コンサルとされた視点から))

    メジカルビュー社  2020.10  ( ISBN:978-4-7583-1811-2

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    Total pages:220   Responsible for pages:99-102   Language:Japanese Book type:General book, introductory book for general audience

  13. 臨床消化器内科:免疫チェックポイント阻害薬による内分泌障害

    小林朋子、岩間信太郎、有馬寛( Role: Joint author)

    日本メディカルセンター  2020.5 

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    Language:Japanese Book type:Scholarly book

  14. 日本内科学会雑誌:特集:内分泌疾患と電解質異常 トピックスⅠ:低ナトリウム血症と内分泌疾患

    岩間信太郎, 有馬寛( Role: Joint author)

    日本内科学会  2020.4 

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    Responsible for pages:705-711   Language:Japanese Book type:Scholarly book

  15. 今日の診断指針第8版:低ナトリウム血症、高ナトリウム血症

    岩間信太郎、有馬寛( Role: Joint author)

    医学書院  2020.3 

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    Language:Japanese Book type:Scholarly book

  16. 癌と化学療法:内分泌障害

    岩間信太郎( Role: Sole author)

    癌と化学療法社  2020.2 

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    Responsible for pages:203-206   Language:Japanese Book type:Scholarly book

  17. 今日の治療指針2020:尿崩症

    岩間信太郎( Role: Sole author)

    医学書院  2020.1 

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    Responsible for pages:802-803   Language:Japanese Book type:Scholarly book

  18. 内科/特集:『内分泌Up To Date』免疫関連副作用としての内分泌障害

    岩間信太郎( Role: Sole author)

    南江堂  2020.1 

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    Responsible for pages:2513-2516   Language:Japanese Book type:Scholarly book

  19. Medical Practice/免疫チェックポイント阻害薬による内分泌障害の診療ガイドラインのポイント

    岩間信太郎、有馬寛( Role: Joint author)

    文光堂  2019.12 

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    Language:Japanese Book type:Scholarly book

  20. 腫瘍内科/免疫チェックポイント阻害と内分泌有害事象

    岩間信太郎( Role: Sole author)

    科学評論社  2019.12 

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    Responsible for pages:666-670   Language:Japanese Book type:Scholarly book

  21. リウマチ科/特集/免疫関連副作用としての自己免疫疾患 内分泌障害

    岩間信太郎( Role: Sole author)

    科学評論社  2019.11 

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    Responsible for pages:435-439   Language:Japanese Book type:Scholarly book

  22. 日本内科学会雑誌/免疫チェックポイント阻害薬-内分泌関連の副作用とその対策

    有馬寛, 小林朋子, 岩間信太郎( Role: Joint author)

    日本内科学会  2019.9 

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    Responsible for pages:1788-1792   Language:Japanese Book type:Scholarly book

  23. 内分泌・糖尿病・代謝内科/免疫チェックポイント阻害薬による下垂体障害

    小林朋子, 岩間信太郎, 有馬寛( Role: Joint author)

    科学評論社  2019.8 

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    Responsible for pages:80-84   Language:Japanese Book type:Scholarly book

  24. 内科学書第9版/下垂体後葉の異常 下垂体後葉疾患

    岩間信太郎, 有馬寛( Role: Joint author)

    中山書店  2019.8 

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    Responsible for pages:63-68   Language:Japanese Book type:Scholarly book

  25. 内科学書第9版/下垂体後葉の異常 下垂体後葉の構造と機能

    岩間信太郎, 有馬寛( Role: Joint author)

    中山書店  2019.8 

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    Responsible for pages:60-62   Language:Japanese Book type:Scholarly book

  26. 内分泌・糖尿病・代謝内科/抗CTLA-4抗体による下垂体炎の発症機序

    岩間信太郎( Role: Sole author)

    科学評論社  2019.8 

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    Responsible for pages:135-137   Language:Japanese Book type:Scholarly book

  27. 私の治療 免疫チェックポイント阻害薬による内分泌代謝異常

    岩間信太郎, 有馬寛( Role: Joint author)

    週刊日本醫事新報  2019.5 

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    Responsible for pages:42-43   Language:Japanese Book type:Scholarly book

  28. 別冊日本臨床 内分泌症候群(第3版)IV/異所性ADH産生腫瘍

    岩間信太郎, 有馬寛( Role: Joint author)

    日本臨床社  2019.3 

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    Responsible for pages:306-309   Language:Japanese Book type:Scholarly book

  29. 日本内分泌学会雑誌:免疫チェックポイント阻害薬による内分泌障害の診療ガイドライン

    日本内分泌学会編( Role: Joint author)

    日本内分泌学会  2018.11 

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    Language:Japanese Book type:Scholarly book

  30. 内分泌・糖尿病・代謝内科・特集/免疫チェックポイント阻害剤における内分泌障害2018/免疫チェックポイント阻害剤による下垂体・副腎障害

    岩間信太郎, 有馬寛( Role: Joint author)

    科学評論社  2018.11 

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    Responsible for pages:402-405   Language:Japanese Book type:Scholarly book

  31. 日本内分泌学会雑誌:免疫チェックポイント阻害薬による内分泌障害の診療ガイドライン

    日本内分泌学会編( Role: Joint author)

    日本内分泌学会  2018.11 

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    Responsible for pages:1-11   Language:Japanese Book type:Scholarly book

  32. 特集/免疫チェックポイント阻害剤における内分泌障害2018/免疫チェックポイント阻害剤による下垂体・副腎障害

    岩間信太郎, 有馬寛( Role: Joint author)

    科学評論社  2018.11 

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    Responsible for pages:402-405   Language:Japanese Book type:Scholarly book

  33. 別冊 医学のあゆみ:がん免疫療法の躍進 免疫チェックポイント阻害薬による下垂体障害・下垂体炎

    岩間信太郎, 有馬寛( Role: Joint author)

    医学のあゆみ  2018.9 

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    Responsible for pages:115-119   Language:Japanese Book type:Scholarly book

  34. 腫瘍内科・抗PD-1抗体による甲状腺障害の特徴と高リスクマーカー

    岩間信太郎, 有馬寛( Role: Joint author)

    科学評論社  2018.8 

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    Responsible for pages:156-160   Language:Japanese Book type:Scholarly book

  35. 臨床免疫・アレルギー科:免疫チェックポイント阻害と下垂体障害

    岩間信太郎, 有馬寛( Role: Joint author)

    科学評論社  2018.6 

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    Responsible for pages:558-562   Language:Japanese Book type:Scholarly book

  36. ここが知りたい! 内分泌疾患診療ハンドブック Ver.2・下垂体炎

    岩間信太郎, 有馬寛( Role: Joint author)

    中外医学社  2018.5 

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    Responsible for pages:160-168   Language:Japanese Book type:Scholarly book

  37. 最新医学・免疫チェックポイント阻害薬による内分泌障害

    岩間信太郎, 有馬寛( Role: Joint author)

    最新医学社  2018.5 

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    Responsible for pages:693-700   Language:Japanese Book type:Scholarly book

  38. 健康への道:トピックス2 がんと免疫

    岩間信太郎, 有馬寛( Role: Joint author)

    名古屋大学総合保健体育科学センター  2018.3 

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    Responsible for pages:2-4   Language:Japanese Book type:Scholarly book

  39. がん免疫療法:免疫チェックポイント阻害剤による内分泌有害事象

    岩間信太郎、有馬寛( Role: Joint author)

    メディカルレビュー社  2018.3 

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    Language:Japanese Book type:Scholarly book

  40. がん免疫療法:免疫チェックポイント阻害剤による内分泌有害事象

    岩間信太郎, 有馬寛( Role: Joint author)

    メディカルレビュー社  2018.3 

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    Responsible for pages:20-24   Language:Japanese Book type:Scholarly book

  41. Expert Opinion for Primary Care:認知症と誤診しやすい内科系疾患 低ナトリウム血症

    岩間信太郎, 有馬寛( Role: Joint author)

    グループ・ティー  2018.3 

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    Responsible for pages:3   Language:Japanese Book type:Scholarly book

  42. 診断と治療:免疫チェックポイント阻害薬による内分泌障害

    小林朋子, 岩間信太郎, 有馬寛( Role: Joint author)

    診断と治療社  2018 

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    Responsible for pages:1127-1132   Language:Japanese Book type:Scholarly book

  43. Keynote R・A:免疫チェックポイント阻害薬による内分泌副作用

    岩間信太郎, 有馬寛( Role: Joint author)

    先端医学社  2017.12 

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    Responsible for pages:114-120   Language:Japanese Book type:Scholarly book

  44. 医学のあゆみ:特集:がん免疫療法の躍進 免疫チェックポイント阻害薬による下垂体障害・下垂体炎

    岩間信太郎, 有馬寛( Role: Joint author)

    医学のあゆみ  2017.10 

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    Responsible for pages:109-113   Language:Japanese Book type:Scholarly book

  45. 医学のあゆみ:特集:免疫チェックポイント阻害療法の副作用と対策マネジメント 抗CTLA-4抗体療法による下垂体障害

    岩間信太郎, 有馬寛( Role: Joint author)

    医学のあゆみ  2017.6 

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    Responsible for pages:1137-1141   Language:Japanese Book type:Scholarly book

  46. カレントテラピー・免疫チェックポイント阻害療法における免疫性有害事象

    岩間信太郎, 有馬寛( Role: Joint author)

    ライフメディコム  2017.2 

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    Responsible for pages:161-165   Language:Japanese Book type:Scholarly book

  47. 日本内分泌学会雑誌:免疫チェックポイント阻害薬による内分泌障害(臨床研究第一報)

    小林朋子, 岩間信太郎, 安田康紀, 岩田尚子, 椙村益久, 安藤雄一, 秋山真志, 長谷川好規, 有馬寛( Role: Joint author)

    日本内分泌学会  2017 

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    Responsible for pages:70-72   Language:Japanese Book type:Scholarly book

  48. 日本臨床免疫学会会誌:免疫チェックポイント阻害剤による内分泌副作用の臨床とそのメカニズム

    岩間信太郎, 有馬寛( Role: Joint author)

    日本臨床免疫学会  2017 

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    Responsible for pages:90-94   Language:Japanese Book type:Scholarly book

  49. 総合保健体育科学:スポーツ頭部外傷に伴う下垂体機能低下症

    岩間信太郎( Role: Sole author)

    名古屋大学総合保健体育科学センター  2016.12 

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    Responsible for pages:1-4   Language:Japanese Book type:Scholarly book

  50. 糖尿病診療ガイドライン2016/運動療法

    押田芳治, 小池晃彦, 岩間信太郎( Role: Joint author)

    南江堂  2016.6 

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    Responsible for pages:67-81   Language:Japanese Book type:Scholarly book

  51. 健康への道:トピックス3 頭を強く打った後で生じるホルモンの異常

    岩間信太郎( Role: Sole author)

    名古屋大学総合保健体育科学センター  2016.3 

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    Responsible for pages:3-4   Language:Japanese Book type:Scholarly book

  52. New専門医を目指すケース・メソッド・アプローチ 内分泌疾患 第3版

    岩間信太郎, 椙村益久( Role: Sole author)

    日本医事新報社  2016.3 

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    Responsible for pages:13-23   Language:Japanese Book type:Scholarly book

  53. 診断と治療:糖尿病教育と多職種連携 有酸素運動とレジスタンス運動

    押田芳治, 小池晃彦, 岩間信太郎( Role: Joint author)

    診断と治療社  2016.3 

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    Responsible for pages:267-272   Language:Japanese Book type:Scholarly book

  54. ホルモンと臨床:AVP (特集 下垂体疾患の診断と治療 : 現状と課題)

    岩間信太郎, 有馬寛( Role: Sole author)

    医学の世界社  2016 

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    Responsible for pages:305-311   Language:Japanese Book type:Scholarly book

  55. CAMPUS HEALTH:名古屋大学における健診データ自動収集システムについて

    石黒洋, 中原久美子, 宮田祐子, 長尾杏子, 千藤ますみ, 市橋淳, 木村千春, 小池晃彦, 山本明子, 岩間信太郎, 押田芳治( Role: Joint author)

    全国大学保健管理協会  2016 

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    Responsible for pages:33-36   Language:Japanese Book type:Scholarly book

  56. 日本内分泌学会雑誌 JES News:リンパ球性漏斗下垂体後葉炎の自己抗原ラブフィリン3Aの同定

    岩間信太郎, 椙村益久( Role: Joint author)

    日本内分泌学会  2015.10 

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    Responsible for pages:157   Language:Japanese Book type:Scholarly book

  57. 糖尿病合併症:糖尿病合併症から考える食事・運動療法 サルコペニア対策としての運動療法

    押田芳治, 小池晃彦, 岩間信太郎, 佐藤祐造( Role: Joint author)

    日本糖尿病合併症学会  2015.6 

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    Responsible for pages:106-109   Language:Japanese Book type:Scholarly book

  58. 総合保健体育科学:自己免疫性下垂体炎の自己抗原の同定と新規診断マーカー開発への挑戦

    岩間信太郎( Role: Sole translator)

    名古屋大学総合保健体育科学センター  2015.5 

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    Responsible for pages:27   Language:Japanese Book type:Scholarly book

  59. 最新医学:トップランナーに聞く 下垂体炎の新規自己抗体の同定と臨床応用への挑戦

    岩間信太郎( Role: Sole author)

    最新医学社  2015.5 

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    Responsible for pages:967-970   Language:Japanese Book type:Scholarly book

  60. 体育の科学・代謝障害の予防・改善

    押田芳治, 小池晃彦, 岩間信太郎( Role: Joint author)

    杏林書院  2015.3 

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    Responsible for pages:183-187   Language:Japanese Book type:Scholarly book

  61. 健康への道:トピックス3 心身の健康維持に重要な下垂体ホルモン

    岩間信太郎( Role: Sole translator)

    名古屋大学総合保健体育科学センター  2014.12 

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    Responsible for pages:4   Language:Japanese Book type:Scholarly book

  62. 内分泌・糖尿病・代謝内科:抗下垂体抗体の評価法とその臨床的意義

    岩間信太郎, 椙村益久, 押田芳治, 大磯ユタカ( Role: Joint author)

    科学評論社  2014 

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    Responsible for pages:69-75   Language:Japanese Book type:Scholarly book

  63. ホルモンと臨床:中枢性尿崩症の病態 (特集 下垂体疾患の診断と治療 : 現状と課題)

    岩間信太郎、椙村益久、大磯ユタカ( Role: Joint author)

    医学の世界社  2010.9 

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    Language:Japanese

▼display all

Presentations 32

  1. 教育セミナー/PD-1阻害、CTLA-4阻害と内分泌機能異常症 Invited

    岩間信太郎

    第34回日本内分泌外科学会総会  2022.6.25  日本内分泌外科学会

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    Event date: 2022.6

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:つくば、Web  

  2. ランチョンセミナー/PD-1阻害、CTLA-4阻害と甲状腺機能異常 Invited

    岩間信太郎

    第95回日本内分泌学会学術総会  2022.6.3  日本内分泌学会

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    Event date: 2022.6

    Language:Japanese  

    Venue:大分、Web  

  3. シンポジウム/免疫チェックポイント阻害薬関連下垂体障害と抗下垂体抗体 Invited

    岩間信太郎、有馬寛

    第95回日本内分泌学会学術総会  2022.6.3  日本内分泌学会

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    Event date: 2022.6

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:大分、Web  

  4. 令和4年度第1回教育セミナー/免疫チェックポイント阻害薬による 内分泌有害事象のバイオマーカーと発症機序 Invited

    岩間信太郎

    日本内科学会東北支部教育セミナー  2022.2.19  日本内科学会

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    Event date: 2022.2

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:Web  

  5. イブニングセミナー/下垂体におけるirAEs Invited

    岩間信太郎

    第19回日本臨床腫瘍学会学術集会  2022.2.18  日本臨床腫瘍学会

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    Event date: 2022.2

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:京都、Web  

  6. ランチョンセミナー/内分泌irAEの特徴と高リスクマーカー Invited

    岩間信太郎

    第109回日本泌尿器科学会総会  2021.12.8  日本泌尿器科学会

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    Event date: 2021.12

    Venue:横浜  

  7. Meet the Expert 1/免疫チェックポイント阻害薬関連 内分泌irAEsのバイオマーカーと発症機序 Invited

    岩間信太郎

    第31回臨床内分泌代謝Update  2021.11.26  日本内分泌学会

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    Event date: 2021.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:大阪+Web  

  8. コスミック研究創成賞受賞講演/抗PD-1抗体誘発破壊性甲状腺炎マウスモデルの開発と発症機序の解明 Invited

    岩間信太郎

    第64回日本甲状腺学会学術集会  2021.11.20  日本甲状腺学会

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    Event date: 2021.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:東京  

  9. 抗PD-1抗体による甲状腺障害の基礎と臨床 Invited

    岩間信太郎

    第64回日本甲状腺学会学術集会  2021.11.19  日本甲状腺学会

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    Event date: 2021.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:東京  

  10. がん免疫療法エキスパートセミナー/「内分泌」 irAEを学ぶ Invited

    岩間信太郎

    日本臨床腫瘍学会がん免疫療法エキスパートセミナー  2021.11.6  日本臨床腫瘍学会

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    Event date: 2021.11

    Language:Japanese  

    Venue:Web  

  11. トランスレーショナルリサーチシンポジウム/抗PD-1抗体、抗CTLA-4抗体による 下垂体機能低下症の病型とバイオマーカー Invited

    岩間信太郎、有馬寛

    第47回日本神経内分泌学会学術集会  2021.10.31  日本神経内分泌学会

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    Event date: 2021.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:奈良  

  12. 川上賞受賞講演/自己免疫が関与する下垂体疾患の研究 Invited

    岩間信太郎

    第47回日本神経内分泌学会学術集会  2021.10.30  日本神経内分泌学会

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    Event date: 2021.10

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:奈良   Country:Japan  

  13. 内分泌障害の臨床像と発症予測 Invited

    岩間信太郎

    第59回日本癌治療学会学術集会  2021.10.22  日本癌治療学会

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    Event date: 2021.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:横浜  

  14. 下垂体炎の鑑別 Invited

    岩間信太郎

    第94回日本内分泌学会学術総会  2021.4.22 

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    Event date: 2021.4

  15. コスミック研究創成賞候補者講演/抗PD-1抗体による破壊性甲状腺炎の 発症に関与するリンパ球分画の同定 Invited

    岩間信太郎

    第63回日本甲状腺学会学術集会  2020.11.20 

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    Event date: 2020.11

    Language:Japanese  

  16. 2020年度 日本内分泌学会研究奨励賞 受賞講演/自己免疫と炎症が関与する 視床下部下垂体疾患の研究 Invited

    岩間信太郎

    第30回臨床内分泌代謝Update  2020.11.13 

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    Event date: 2020.11

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

  17. 免疫チェックポイント製剤使用時における irAEマネジメント ~内分泌障害に関して・内分泌代謝科専門医の立場から~ Invited

    岩間信太郎

    第58回日本癌治療学会学術集会  2020.10.23 

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    Event date: 2020.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  18. 免疫チェックポイント阻害薬による内分泌障害 ~甲状腺障害・下垂体障害・1型糖尿病の対処法~ Invited

    岩間信太郎

    第28回日本乳癌学会学術総会  2020.10.9 

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    Event date: 2020.10

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

  19. シンポジウム21「薬剤性甲状腺機能異常の基礎と臨床」/免疫チェックポイント阻害薬による 甲状腺機能異常 Invited

    岩間信太郎、有馬寛

    第93回日本内分泌学会学術総会  2020.6.6 

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    Event date: 2020.6

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  20. 免疫チェックポイント阻害剤による 内分泌有害事象のマネジメント-名古屋大学医学部附属病院での取組み- Invited

    岩間信太郎

    第60回日本肺癌学会学術集会  2019.12.7 

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    Event date: 2019.12

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  21. シンポジウム 03:免疫治療の有害事象対策/内分泌関連の有害事象とその対策 Invited

    岩間信太郎

    第60回日本肺癌学会学術集会  2019.12.6 

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    Event date: 2019.12

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:大阪  

  22. 免疫チェックポイント阻害薬による 甲状腺機能異常症の 臨床像、高リスク因子、発症機序 Invited

    岩間信太郎

    第29回臨床内分泌代謝 Update in Kochi  2019.11.29 

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    Event date: 2019.11

    Language:Japanese  

    Venue:高知  

  23. シンポジウム41 /『免疫チェックポイント阻害薬使用 (ICI) における注意点』/内科医の立場から: 知っておくべき内分泌副作用と対処法 Invited

    岩間信太郎

    第73回国立病院総合医学会  2019.11.8 

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    Event date: 2019.11

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:名古屋  

  24. Plenary Session/Adverse events in pituitary and thyroid glands induced by immune checkpoint inhibitors. Invited

    Shintaro Iwama

    The 7th Annual Meeting of the International Cytokine & Interferon Society (Cytokines 2019), Vienna  2019.10.20 

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    Event date: 2019.10

    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Vienna  

  25. 免疫チェックポイント阻害薬による下垂体機能低下症の基礎と臨床 Invited

    岩間信太郎, 有馬寛

    第92回日本内分泌学会学術総会  2019.5 

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    Event date: 2019.5

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  26. 日韓内分泌学会特別口演セッション/Plenary Oral Session/Anti-pituitary antibodies in pituitary diseases Invited International conference

    Shintaro Iwama

    第92回日本内分泌学会学術総会  2019.5 

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    Event date: 2019.5

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  27. 特別企画/免疫チェックポイント阻害療法における内分泌障害の病態とバイオマーカー Invited

    岩間信太郎, 有馬寛

    第33回日本臨床リウマチ学会  2018.11.25 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  28. Mechanisms and managements of adverse events induced by immune checkpoint inhibitors in pituitary and thyroid glands Invited

    2018.5.19 

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    Event date: 2018.5

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  29. 免疫チェックポイント阻害薬による下垂体障害・副腎障害 Invited

    岩間信太郎, 有馬寛

    第91回日本内分泌学会学術総会  2018.4 

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    Event date: 2018.4

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  30. WS1-3 免疫チェックポイント阻害薬による下垂体障害・下垂体炎 Invited International conference

    岩間 信太郎, 有馬 寛

    日本臨床免疫学会  2017.9.28  日本臨床免疫学会会誌

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    Event date: 2017.9

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    <p>  免疫チェックポイント阻害薬で認められる免疫関連有害事象(immune-related adverse events; irAEs)は全身の臓器で認められ,大腸炎,肝炎,間質性肺炎,皮膚炎,神経・筋障害,内分泌障害などが報告されている.死亡に至る重篤例もあることから適切な対応が重要である.irAEsとして障害される内分泌器官は下垂体,甲状腺,副腎皮質,膵,副甲状腺が挙げられ,それぞれ異なる対応を要する.下垂体障害の頻度は細胞傷害性T細胞抗原(cytotoxic T-lymphocyte-associated antigen; CTLA)-4に対する抗体であるイピリムマブで4-10%程度,programmed cell death(PD)-1に対する抗体で1%未満と報告されている.下垂体前葉機能障害および下垂体腫大を呈する症例は臨床的に下垂体炎と考えられる.内分泌学的には副腎皮質刺激ホルモン(ACTH)の障害が最も高頻度で認められ,診断が遅れると副腎クリーゼとなり得る重篤な副作用である.これまでに報告された抗PD-1抗体または抗CTLA-4抗体による下垂体障害・下垂体炎の症例を検討した結果,両者の臨床的特徴には相違点があることが解ってきた.本講演では,抗PD-1抗体または抗CTLA-4抗体による下垂体障害・下垂体炎について臨床的特徴をそれぞれ解説し,両者の相違点について考察する.</p>

  31. 免疫チェックポイント阻害薬による内分泌系免疫関連副作用 Invited International conference

    岩間信太郎

    第29回日本内分泌外科学会総会 特別講演  2017.5.19 

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    Event date: 2017.5

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  32. WS2-4 免疫チェックポイント阻害剤による内分泌副作用の臨床とそのメカニズム Invited

    岩間 信太郎, 有馬 寛

    日本臨床免疫学会  2016.9.8  日本臨床免疫学会会誌

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    Event date: 2016.9

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    <p>  免疫チェックポイント阻害剤はT細胞の活性化を負に制御する分子に対するモノクローナル抗体で,細胞傷害性T細胞抗原(CTLA)4に対する抗体であるイピリムマブ(Ipi)とprogrammed cell death-1に対する抗体であるニボルマブが本邦でも近年使用開始された.これらの薬剤は,優れた抗腫瘍効果の一方で,自己免疫機序が想定される重篤な副作用を発症させ,特に,肝炎,腸炎,皮膚炎,内分泌障害が好発する.内分泌副作用として,下垂体炎,甲状腺機能異常症,副腎炎,1型糖尿病などが報告されており,薬剤によりその発症頻度は異なる.特に我々は,従来まれな疾患と考えられてきた下垂体炎が,Ipi使用者において約10%もの頻度で発症することに着目し,抗マウスCTLA4抗体をSJLマウスに連続投与することで下垂体に炎症細胞浸潤を呈する抗CTLA4抗体誘発下垂体炎マウスモデルを作成した.本マウスにおける病態解析を進め,抗CTLA4抗体は下垂体に発現するCTLA4に直接結合し,補体活性化を介したII型アレルギー反応により下垂体に炎症を誘発する可能性を報告した.さらに,Ipiにより下垂体炎を発症した患者血清中に抗下垂体抗体が存在することを明らかにし,臨床における抗下垂体抗体の診断的有用性を示した.本講演では抗CTLA4抗体による下垂体炎の発症メカニズムおよび実際の症例を紹介するとともに,現在名古屋大学で行っている臨床研究についても紹介したい.</p>

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Works 6

  1. がん免疫治療薬により発症する下垂体副作用の事前予測が可能に(名古屋大学プレスリリース)

    2021.5

  2. 抗 PD-1 抗体による甲状腺副作用の発症メカニズムをマウスで解明(名古屋大学プレスリリース)

    岩間信太郎

    2021.5

  3. がん免疫治療薬によって下垂体に副作用が発生した場合、生存期間が延長することを発見(名古屋大学プレスリリース)

    2020.7

  4. がん免疫治療薬ニボルマブ(オプジーボ®)による甲状腺副作用の高リスク患者を、治療前に判別できる指標を解明(名古屋大学プレスリリース)

    2018.2

  5. リンパ球性漏斗下垂体後葉炎の自己抗原をはじめて同定 ~血液検査による診断法の確立に期待~(名古屋大学プレスリリース)

    2015.5

  6. 抗CTLA-4阻害抗体を用いた腫瘍免疫療法に併発する二次性下垂体炎の発症機序の解明(名古屋大学プレスリリース)

    2014.4

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Research Project for Joint Research, Competitive Funding, etc. 5

  1. 免疫チェックポイント阻害薬による下垂体障害のバイオマーカー開発

    2020.7 - 2021.3

    公益財団法人愛知県がん研究振興会  第45回がんその他の悪性新生物研究助成金 

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    Authorship:Principal investigator  Grant type:Competitive

  2. がん免疫療法に伴う免疫関連副作用の病態解明

    2017 - 2018

    公益財団法人 上原記念生命科学財団 平成28年度 研究奨励金 

    岩間信太郎

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    Grant type:Competitive

  3. がん免疫チェックポイント阻害薬による自己免疫性内分泌副作用に関連する新規自己抗体の網羅的解析

    2016.10 - 2018.10

    公益財団法人 豊秋奨学会 平成28年度 研究費助成 

    岩間信太郎

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    Grant type:Competitive

  4. 自己免疫性視床下部下垂体後葉炎の新規自己抗体である抗ラブフィリン3a抗体による診断キット用ELISAの開発に関する研究

    2015.4 - 2016.3

    公益財団法人市原国際奨学財団 第23回(平成27年度) 研究助成 

    岩間信太郎

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    Grant type:Competitive

  5. Comparison of the utility to measure anti-pituitary antibodies by using human or rat pituitary substrate in patients with biopsy-proven lymphocytic hypophysitis

    2014.12 - 2015.11

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. Study of identification for autoantigens in a mouse model of pituitary dysfunction induced by CTLA-4 or PD-1 blockade

    Grant number:22K08648  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  2. Establishment of the system for predicting pituitary dysfunction induced by immune checkpoint inhibitors

    Grant number:22H03127  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s) 

  3. 抗PD-1抗体誘発甲状腺炎マウスモデルを用いた免疫関連有害事象の発症機序の解明

    Grant number:19K08976  2019.4 - 2022.3

    基盤研究(C)

    岩間 信太郎

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    免疫チェックポイント阻害薬を用いたがん免疫療法では、自己免疫機序が想定される免疫関連有害事象(irAEs)の発生が課題であるが、発症機序は不明で、有用な動物モデルもないのが現状である。最も広く使用されている抗PD-1抗体では、irAEsとして甲状腺機能異常症の頻度が高い。
    本課題では、抗PD-1抗体誘発甲状腺炎マウスモデルを開発し、甲状腺irAEs発症に関与する特異的リンパ球を同定する。甲状腺およびその他のirAEs患者検体においてマウスモデルの結果を検証し、ヒトのirAEsに共通する炎症発症機構を解明する。
    irAEsの発症機序を解明し、がん免疫療法の発展および自己免疫疾患の病態解明へ繋げる。

  4. Effect of aerobic training and EPA on skeletal muscle in metabolic syndrome

    Grant number:17K01842  2017.4 - 2020.3

    Koike Teruhiko

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Sarcopenic obesity is a condition in which muscle mass loss due to aging and visceral fat accumulation coexist. We investigated whether chronic inflammation due to obesity causes a decrease in skeletal muscle synthesis and a muscle mass loss in a diet-induced obesity model and an aging-promoting model. The effect of aerobic exercise on the changes in muscle mass was also tested. Chronic inflammation and insulin resistance increase in obesity and aging, but the administration of a high-fat diet did not cause a decrease in skeletal muscle synthesis, and the combination with aerobic exercise by spinning wheel increased muscle mass. Therefore, a combination of high-fat diet and aerobic exercise may be effective in preventing sarcopenia, but such intervention should not increase ectopic fat in muscle or metabolic abnormalities.

  5. Elucidation of effects of chronic hyponatremia associated with SIADH on the central nervous system and development of novel therapeutic agents

    Grant number:17K09879  2017.4 - 2020.3

    Sugimura Yoshihisa

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Hyponatremia is a common electrolyte disorder. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a primary cause of hyponatremia. Recently, chronic hyponatremia, even mild, has shown to be associated with poor quality of life and high mortality. The mechanism by which hyponatremia contributes to those symptoms, however, remains to be elucidated. Appropriate animal models are crucial for investigating the pathophysiology of SIADH. In this study, we developed a mouse model of chronic SIADH in which stable and sustained hyponatremia. Behavioral analyses demonstrated cognitive impairment, especially working memory impairment, in chronic SIADH mice, which was partially restored after correcting hyponatremia. Our results suggest that chronic hyponatremia contributed to their memory impairment.

  6. Research for the pathogenesis of hypophysitis induced by immune checkpoint inhibitors

    Grant number:16K19552  2016.4 - 2019.3

    Iwama Shintaro

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    In this study, we tried to make a novel mouse model for hypophysitis which is one of immune related adverse events (irAEs) induced by immune checkpoint inhibitors through the repeated injection with anti-CTLA-4 antibody or anti-PD-1 antibody. We also tried to make a mouse model for thyroiditis as another irAEs model. Finally, we established a novel mouse model which developed destructive thyroiditis after the administration of anti-PD-1 antibody. Using this model, we clarified the cells expressing PD-1 and PD-L1 in the inflamed thyroid glands.
    These findings lead to clarify not only the pathogenesis of irAEs induced by immune checkpoint inhibitors but also the mechanisms of autoimmune diseases in endocrine organs.

  7. Research for autoantigens and autoantibodies in IgG4-related hypophysitis

    Grant number:26893106  2014.8 - 2016.3

    Iwama Shintaro

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2990000 ( Direct Cost: \2300000 、 Indirect Cost:\690000 )

    This study clarified that human pituitary glands were better than rat as substrate to find anti-pituitary antibodies. We also clarified the presence of specific autoantibodies against pituitary glands in IgG4-related hypophysitis (IgG4-RH). These findings lead to establish a novel biomaker for IgG4-RH.

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Media Coverage 4

  1. 下垂体に副作用 生存期間「長く」/中日新聞 Newspaper, magazine

    中日新聞  中日新聞  2020.7

  2. がん患者 生存長く 治療薬投与 下垂体に副作用で/日本経済新聞 Newspaper, magazine

    日本経済新聞社  日本経済新聞  日本経済新聞  2020.7

  3. オプジーボ副作用 発生リスクを判別/中日新聞 Newspaper, magazine

    中日新聞  中日新聞  2018.2

  4. 特有のたんぱく質発見 名古屋大 脳の難病患者から/日経産業新聞 Newspaper, magazine

    日経産業新聞  日経産業新聞  日経産業新聞  2015.5