Tokushima University / Educator and Researcher Directory --- Harada, Takeshi

Personal Web Page

https://researchmap.jp/_haradat (researchmap)

Field of Study

○	Hematology

Subject of Study

○	(Multiple myeloma)

Book / Paper

Book:

1.	Takeshi Harada and Masahiro Abe : くすぶり型多発性骨髄腫別冊日本臨牀領域別症候群シリーズ No.30 血液症候群(第3版)-その他の血液疾患を含めて V, 2024.
2.	Takeshi Harada and Masahiro Abe : 最新の骨粗鬆症学(第2版), NIPPONRINSHOSHA Co.,Ltd., Tokyo, Jan. 2023.
3.	Takeshi Harada and Masahiro Abe : VII. 骨粗鬆症の類縁疾患の診断と治療. 多発性骨髄腫. 最新の骨粗鬆症学 (第2版) -骨粗鬆症の最新知見-, 2023.
4.	Takeshi Harada and Masahiro Abe : I章近年承認された抗がん薬-13．ダラツムマブ・ボルヒアルロニダーゼアルファ配合(ダラキューロ). 最新のがん薬物療法 2023-2024, 2023.
5.	Takeshi Harada : III. 基礎研究 2. 骨髄腫細胞におけるエピゲノム異常多発性骨髄腫 update -診断・治療の最新動向-, 2023.
6.	Takeshi Harada and Masahiro Abe : 専門医のための血液病学, IGAKU-SHOIN Ltd.Tokyo,Japan, Mar. 2022.
7.	Takeshi Harada and Masahiro Abe : 多発性骨髄腫, 2022.
8.	Kumiko Kagawa, 前田悠作, Masahiro Oura, Kimiko Sogabe, 藤野ひかる, 髙橋真美子, 丸橋朋子, 岩佐昌美, 宇高憲吾, Takeshi Harada, Takayuki Ise, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Shusuke Yagi, Kyoko Takeuchi, Shuji Ozaki, Masahiro Abe and 藤野ひかる : Analysis of long-term survivors with cardiac AL amyloidosis, The Japanese Society of Hematology, Oct. 2017. (Summary) <p>Cardiac AL amyloidosis (CA) is generally known as a severe disease with very poor prognosis. Here we retrospectively examined seven patients with CA in our cohort who achieved long-term survival. All six patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT) survived for >3 years, whereas four patients survived for >5 years. Patients who underwent ASCT had prompt hematological responses, and five patients showed organ responses. ASCT helps to achieve a quick and deep hematological response required for long-term survival in patients with CA. New agents have been implemented for the treatment of CA. However, the risks and benefits of each treatment modality should be considered according to patient condition, thus making the best use of ASCT in combination with new agents for the treatment of CA.</p> (Keyword) Cardiac AL amyloidosis / Autologous hematopoietic stem cell transplantation / Long-term survival (Link to Publication Site) ● Publication site (DOI): 10.11406/rinketsu.58.2197 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282680011466240 ● Search Scopus @ Elsevier (DOI): 10.11406/rinketsu.58.2197 (DOI: 10.11406/rinketsu.58.2197, CiNii: 1390282680011466240)

Academic Paper (Judged Full Paper):

1.	Mamiko Takahashi, Shin Kondo, Kumiko Kagawa, Masafumi Nakamura, Yusaku Maeda, Ryohei Sumitani, Hikaru Yagi, Masahiro Oura, Kimiko Sogabe, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Itsuro Endo, Masahiro Abe and Shingen Nakamura : Skeletal muscle mass during chemotherapy for haematological malignancies: a retrospective study., BMJ Supportive & Palliative Care, Vol.14, No.2, 195-199, 2024. (Summary) This study investigated whether baseline or alteration in muscle mass affects complications during chemotherapy or overall survival (OS) in haematological malignancies. Skeletal Muscle Index (SMI) was evaluated by bioimpedance analysis before and after chemotherapy in patients with haematological malignancies, and the association between muscle mass and clinical data was retrospectively analysed. Exactly 104 patients were enrolled, with a mean age of 62.2 years. SMI was 7.85 and 6.08 in male and female patients under 65 years and 7.10 and 5.92 over 65 years, before chemotherapy, respectively. Lower baseline SMI was not correlated with worse OS in total patients (p=0.915). After a median measurement interval of 30 days after chemotherapy (n=67), body weight and SMI decreased by 2.73% and 2.87% (mean), respectively. The decrease in body weight correlated with the loss of trunk muscle mass (R=0.2107) but was more strongly associated with the loss of lower limbs muscle mass (R=0.3985). The muscle mass of lower limbs significantly decreased in lymphoma patients who experienced febrile neutropenia (-0.42% vs -6.04%, p=0.040). OS significantly decreased in lymphoma patients with loss of lower limbs muscle ≥2.8% (p=0.0327). Muscle loss occurred following anticancer treatments, significantly contributing to worse outcomes. Body composition assessment and relevant multimodal prevention of muscle loss may be vital for patients receiving chemotherapy for haematological malignancies. (Keyword) Humans / Male / Female / Retrospective Studies / Middle Aged / Hematologic Neoplasms / Muscle, Skeletal / Aged / Adult / Antineoplastic Agents / Aged, 80 and over / Body Composition / Sarcopenia (Tokushima University Institutional Repository) ● Metadata: 119635 (Link to Publication Site) ● Publication site (DOI): 10.1136/spcare-2024-004870 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38569748 ● Search Scopus @ Elsevier (PMID): 38569748 ● Search Scopus @ Elsevier (DOI): 10.1136/spcare-2024-004870 (Tokushima University Institutional Repository: 119635, DOI: 10.1136/spcare-2024-004870, PubMed: 38569748)
2.	Shingen Nakamura, Keijiro Hara, Tomoko Kobayashi, Ryohei Sumitani, Masahiro Oura, Yusaku Maeda, Kimiko Sogabe, Hikaru Yagi, Mamiko Takahashi, Shiroh Fujii, Takeshi Harada, Yoshimi Bando, Masahiro Abe and Hirokazu Miki : Tl uptake and retention mimicking malignant lymphoma in a patient with human immunodeficiency virus infection., Parasitology International, Vol.101, 102895, 2024. (Summary) Various opportunistic infections develop during immunodeficiency due to human immunodeficiency virus (HIV) infection. The treatment options for malignant lymphoma (ML) and toxoplasmic encephalitis (TE) are completely different; therefore, their discrimination is critical. A 25-year-old female of foreign nationality had been experiencing headaches for several weeks and suddenly developed convulsions. Brain computed tomography revealed multiple intracranial lesions; therefore, the patient was referred to the neurosurgery department. Brain magnetic resonance imaging (MRI) revealed multiple masses with surrounding edema, accompanied by enhanced contrast. The largest mass (2 cm) in the left occipital lobe exhibited ringed contrast enhancement. Her blood test results showed a CD4 count of 40/μL, positive HIV Ag/Ab, HIV-RNA level of 56 × 10 copies/mL, positive anti-Toxoplasma IgG (63 IU/mL), and negative anti-Toxoplasma IgM. Tl- single photon emission computed tomography (Tl-SPECT) revealed abnormal accumulation only in the tumor in the left occipital lobe (early T/N ratio, 3.034; delayed T/N ratio, 2.738; retention index, 0.9), which was suspected to be a ML. Both tumors, with or without high accumulation of Tl, were subjected to craniotomy biopsy. Pathological examination revealed infiltration of small lymphocytes with a necrotic background. The patient was diagnosed with TE based on a positive result of a tissue polymerase chain reaction test for Toxoplasma gondii. Two weeks after sulfamethoxazole and trimethoprim combination therapy, MRI imaging showed dramatic improvement in multiple brain tumors. This case is atypical because ML was ruled out despite high Tl-SPECT uptake and retention. Careful diagnosis through pathological examination and DNA testing is important. (Keyword) Humans / Female / Adult / Toxoplasmosis, Cerebral / Lymphoma / HIV Infections / Magnetic Resonance Imaging / Diagnosis, Differential / Tomography, Emission-Computed, Single-Photon / Toxoplasma (Tokushima University Institutional Repository) ● Metadata: 119634 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.parint.2024.102895 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38614255 ● Search Scopus @ Elsevier (PMID): 38614255 ● Search Scopus @ Elsevier (DOI): 10.1016/j.parint.2024.102895 (Tokushima University Institutional Repository: 119634, DOI: 10.1016/j.parint.2024.102895, PubMed: 38614255)
3.	Minae Hosoki, HORI Taiki, KANEKO Yohsuke, Kensuke Mori, Saya Yasui, Seijiro Tsuji, Hiroki Yamagami, Saki Kawata, Tomoyo Hara, Shiho Masuda, Yukari Mitsui, Kiyoe Kurahashi, Takeshi Harada, Shingen Nakamura, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Itsuro Endo, Munehide Matsuhisa and Ken-ichi Aihara : Causes of In-Hospital Death and Pharmaceutical Associations with Age of Death during a 10-Year Period (2011-2020) in Individuals with and without Diabetes at a Japanese Community General Hospital., Journal of Clinical Medicine, Vol.13, No.5, 1283, 2024. (Summary) Since diabetes and its complications have been thought to exaggerate cardiorenal disease, resulting in a short lifespan, we investigated causes of death and lifespans in individuals with and without diabetes at a Japanese community general hospital during the period from 2011 to 2020. Causes of death and age of death in individuals with and those without diabetes were compared, and associations between medications used and age of death were statistically analyzed. A total of 2326 deaths were recorded during the 10-year period. There was no significant difference between the mean ages of death in individuals with and those without diabetes. Diabetic individuals had higher rates of hepato-pancreatic cancer and cardio-renal failure as causes of death. The prescription rates of antihypertensives, antiplatelets, and statins in diabetic individuals were larger than those in non-diabetic individuals. Furthermore, the use of sulfonyl urea or glinides and insulin was independently and inversely associated with the age of death. In conclusion, individuals with diabetes were treated with comprehensive pharmaceutical interventions and had life spans comparable to those of individuals without diabetes. This study's discovery of an inverse relationship between the use of insulin secretagogues or insulin and the age of death suggests that the prevention of life-threatening hypoglycemia is crucial for individuals with diabetes. (Tokushima University Institutional Repository) ● Metadata: 119252 (Link to Publication Site) ● Publication site (DOI): 10.3390/jcm13051283 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38592103 ● Search Scopus @ Elsevier (PMID): 38592103 ● Search Scopus @ Elsevier (DOI): 10.3390/jcm13051283 (Tokushima University Institutional Repository: 119252, DOI: 10.3390/jcm13051283, PubMed: 38592103)
4.	Tomoko Maruhashi, Hirokazu Miki, Kimiko Sogabe, Asuka Oda, Ryohei Sumitani, Masahiro Oura, Mamiko Takahashi, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Kiyoe Kurahashi, Itsuro Endo and Masahiro Abe : Acute suppression of translation by hyperthermia enhances anti-myeloma activity of carfilzomib, International Journal of Hematology, Vol.119, No.3, 291-302, 2024. (Summary) Hyperthermia is a unique treatment option for cancers. Multiple myeloma (MM) remains incurable and innovative therapeutic options are needed. We investigated the efficacy of hyperthermia and carfilzomib in combination against MM cells. Although MM cell lines exhibited different susceptibilities to pulsatile carfilzomib treatment, mild hyperthermia at 43℃ induced MM cell death in all cell lines in a time-dependent manner. Hyperthermia and carfilzomib cooperatively induced MM cell death even under suboptimal conditions. The pro-survival mediators PIM2 and NRF2 accumulated in MM cells due to inhibition of their proteasomal degradation by carfilzomib; however, hyperthermia acutely suppressed translation in parallel with phosphorylation of eIF2α to reduce these proteins in MM cells. Recovery of β5 subunit enzymatic activity from its immediate inhibition by carfilzomib was observed at 24 h in carfilzomib-insusceptible KMS-11, OPM-2, and RPMI8226 cells, but not in carfilzomib-sensitive MM.1S cells. However, heat treatment suppressed the recovery of β5 subunit activity in these carfilzomib-insusceptible cells. Therefore, hyperthermia re-sensitized MM cells to carfilzomib. Our results support the treatment of MM with hyperthermia in combination with carfilzomib. Further research is warranted on hyperthermia for drug-resistant extramedullary plasmacytoma. (Keyword) Humans / Multiple Myeloma / Oligopeptides / Hyperthermia, Induced (Tokushima University Institutional Repository) ● Metadata: 119321 (Link to Publication Site) ● Publication site (DOI): 10.1007/s12185-023-03706-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38252236 ● Search Scopus @ Elsevier (PMID): 38252236 ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-023-03706-8 (Tokushima University Institutional Repository: 119321, DOI: 10.1007/s12185-023-03706-8, PubMed: 38252236)
5.	Kimiko Sogabe, Shingen Nakamura, Yoshiki Higa, Hirokazu Miki, Asuka Oda, Tomoko Maruhashi, Ryohei Sumitani, Masahiro Oura, Mamiko Takahashi, Masafumi Nakamura, Yusaku Maeda, Tomoyo Hara, Hiroki Yamagami, Shiroh Fujii, Kumiko Kagawa, Shuji Ozaki, Kiyoe Kurahashi, Itsuro Endo, Ken-ichi Aihara, Emiko Nakaue, Masahiro Hiasa, Jumpei Teramachi, Takeshi Harada and Masahiro Abe : Acute accumulation of PIM2 and NRF2 and recovery of β5 subunit activity mitigate multiple myeloma cell susceptibility to proteasome inhibitors., International Journal of Hematology, Vol.119, No.3, 303-315, 2024. (Summary) Resistance to proteasome inhibitors (PIs) has emerged as an important clinical issue. We investigated the mechanisms underlying multiple myeloma (MM) cell resistance to PIs. To mimic their pharmacokinetic/pharmacodynamic (PK/PD) profiles, MM cells were treated with bortezomib and carfilzomib for 1 h at concentrations up to 400 and 1,000 nM, respectively. Susceptibility to these PIs markedly varied among MM cell lines. Pulsatile treatments with PIs suppressed translation, as demonstrated by incorporation of puromycin at 24 h in PI-susceptible MM.1S cells, but not PI-resistant KMS-11 cells. Inhibition of β5 subunit activity decreased at 24 h in KMS-11 cells, even with the irreversible PI carfilzomib, but not under suppression of protein synthesis with cycloheximide. Furthermore, the proteasome-degradable pro-survival factors PIM2 and NRF2 acutely accumulated in MM cells subjected to pulsatile PI treatments. Accumulated NRF2 was trans-localized into the nucleus to induce the expression of its target gene, HMOX1, in MM cells. PIM and Akt inhibition restored the anti-MM effects of PIs, even against PI-resistant KMS-11 cells. Collectively, these results suggest that increased synthesis of β5 proteasome subunit and acute accumulation of PIM2 and NRF2 reduce the anti-MM effects of PIs. (Keyword) Humans / Proteasome Inhibitors / NF-E2-Related Factor 2 / Multiple Myeloma / Proteasome Endopeptidase Complex / Drug Resistance, Neoplasm / Cell Line, Tumor / Bortezomib / Antineoplastic Agents / Proto-Oncogene Proteins / Protein Serine-Threonine Kinases (Tokushima University Institutional Repository) ● Metadata: 119384 (Link to Publication Site) ● Publication site (DOI): 10.1007/s12185-023-03705-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38245883 ● Search Scopus @ Elsevier (PMID): 38245883 ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-023-03705-9 (Tokushima University Institutional Repository: 119384, DOI: 10.1007/s12185-023-03705-9, PubMed: 38245883)
6.	Hiroki Yamagami, Tomoyo Hara, Saya Yasui, Minae Hosoki, Taiki Hori, Yousuke Kaneko, Yukari Mitsui, Kiyoe Kurahashi, Takeshi Harada, Sumiko Yoshida, Shingen Nakamura, Toshiki Otoda, Tomoyuki Yuasa, Akio Kuroda, Itsuro Endo, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : Cross-Sectional and Longitudinal Associations between Skin Autofluorescence and Tubular Injury Defined by Urinary Excretion of Liver-Type Fatty Acid-Binding Protein in People with Type 2 Diabetes., Biomedicines, Vol.11, No.11, 3020, 2023. (Summary) = 0.026). In conclusion, SAF is positively correlated with uL-FABP but not with uACR in people with T2D. Thus, there is a possibility that SAF can serve as a novel predictor for the development of diabetic tubular injury. (Keyword) skin autofluorescence / type 2 diabetes / diabetic kidney disease / albuminuria / tubular injury / L-FABP (Tokushima University Institutional Repository) ● Metadata: 119108 (Link to Publication Site) ● Publication site (DOI): 10.3390/biomedicines11113020 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38002020 ● CiNii @ National Institute of Informatics (CRID): 1870302167614368000 ● Summary page in Scopus @ Elsevier: 2-s2.0-85178346619 (Tokushima University Institutional Repository: 119108, DOI: 10.3390/biomedicines11113020, PubMed: 38002020, CiNii: 1870302167614368000, Elsevier: Scopus)
7.	Saya Yasui, Yousuke Kaneko, Hiroki Yamagami, Minae Hosoki, Taiki Hori, Akihiro Tani, Tomoyo Hara, Kiyoe Kurahashi, Takeshi Harada, Shingen Nakamura, Toshiki Otoda, Tomoyuki Yuasa, Hiroyasu Mori, Akio Kuroda, Itsuro Endo, Munehide Matsuhisa, Takeshi Soeki and Ken-ichi Aihara : Dehydroepiandrosterone Sulfate, an Adrenal Androgen, Is Inversely Associated with Prevalence of Dynapenia in Male Individuals with Type 2 Diabetes., Metabolites, Vol.13, No.11, 1129, 2023. (Summary) Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia. (Tokushima University Institutional Repository) ● Metadata: 119107 (Link to Publication Site) ● Publication site (DOI): 10.3390/metabo13111129 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37999225 ● CiNii @ National Institute of Informatics (CRID): 1870583643033891840 ● Summary page in Scopus @ Elsevier: 2-s2.0-85178271509 (Tokushima University Institutional Repository: 119107, DOI: 10.3390/metabo13111129, PubMed: 37999225, CiNii: 1870583643033891840, Elsevier: Scopus)
8.	Masahiro Oura, Takeshi Harada, Asuka Oda, Jumpei Teramachi, Atsushi Nakayama, Ryohei Sumitani, Yusuke Inoue, Yusaku Maeda, Kimiko Sogabe, Maruhashi Tomoko, Mamiko Takahashi, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Shingen Nakamura, Tomoyo Hara, Hiroki Yamagami, Kiyoe Kurahashi, Itsuro Endo, Hiroo Hasegawa, Hiroshi Fujiwara and Masahiro Abe : Therapeutic efficacy of the resorcylic acid lactone LL-Z1640-2 for adult T-cell leukaemia/lymphoma, eJHaem, Vol.4, No.3, 667-678, 2023. (Summary) Adult T-cell leukaemia/lymphoma (ATL) remains incurable. The NF-κB and interferon regulatory factor 4 (IRF4) signalling pathways are among the critical survival pathways for the progression of ATL. TGF-β-activated kinase 1 (TAK1), an IκB kinase-activating kinase, triggers the activation of NF-κB. The resorcylic acid lactone LL-Z1640-2 is a potent irreversible inhibitor of TAK1/extracellular signal-regulated kinase 2 (ERK2). We herein examined the therapeutic efficacy of LL-Z1640-2 against ATL. LL-Z1640-2 effectively suppressed the in vivo growth of ATL cells. It induced in vitro apoptosis and inhibited the nuclear translocation of p65/RelA in ATL cells. The knockdown of strongly induced ATL cell death while downregulating MYC. LL-Z1640-2 as well as the NF-κB inhibitor BAY11-7082 decreased the expression of IRF4 and MYC at the protein and mRNA levels, indicating the suppression of the NF-κB-IRF4-MYC axis. The treatment with LL-Z1640-2 also mitigated the phosphorylation of p38 MAPK along with the expression of CC chemokine receptor 4. Furthermore, the inhibition of STAT3/5 potentiated the cytotoxic activity of LL-Z1640-2 against IL-2-responsive ATL cells in the presence of IL-2. Therefore, LL-Z1640-2 appears to be an effective treatment for ATL. Further studies are needed to develop more potent compounds that retain the active motifs of LL-Z1640-2. (Link to Publication Site) ● Publication site (DOI): 10.1002/jha2.758 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37601887 ● Search Scopus @ Elsevier (PMID): 37601887 ● Search Scopus @ Elsevier (DOI): 10.1002/jha2.758 (DOI: 10.1002/jha2.758, PubMed: 37601887)
9.	Shiho Masuda, Tomoyo Hara, Hiroki Yamagami, Yukari Mitsui, Kiyoe Kurahashi, Sumiko Yoshida, Takeshi Harada, Toshiki Otoda, Tomoyuki Yuasa, Shingen Nakamura, Akio Kuroda, Itsuro Endo, Toshio Matsumoto, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : Vascular Endothelial Function Is Associated with eGFR Slope in Female and Non-Smoking Male Individuals with Cardiovascular Risk Factors: A Pilot Study on the Predictive Value of FMD for Renal Prognosis., Journal of Atherosclerosis and Thrombosis, 2023. (Summary) In individuals with cardiovascular risk factors, evaluation of vascular endothelial function enables prediction of renal prognosis in females and non-smoking males. (Tokushima University Institutional Repository) ● Metadata: 118250 (Link to Publication Site) ● Publication site (DOI): 10.5551/jat.63987 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37081616 ● Search Scopus @ Elsevier (PMID): 37081616 ● Search Scopus @ Elsevier (DOI): 10.5551/jat.63987 (Tokushima University Institutional Repository: 118250, DOI: 10.5551/jat.63987, PubMed: 37081616)
10.	Emiko Nakaue, Jumpei Teramachi, Hirofumi Tenshin, Masahiro Hiasa, Takeshi Harada, Asuka Oda, Yusuke Inoue, Sou Shimizu, Yoshiki Higa, Kimiko Sogabe, Masahiro Oura, Tomoyo Hara, Ryohei Sumitani, Tomoko Maruhashi, Hiroki Yamagami, Itsuro Endo, Eiji Tanaka and Masahiro Abe : Mechanisms of preferential bone formation in myeloma bone lesions by proteasome inhibitors., International Journal of Hematology, 2023. (Summary) Proteasome inhibitors (PIs) can preferentially restore bone in bone-defective lesions of patients with multiple myeloma (MM) who respond favorably to these drugs. Most prior in vitro studies on PIs used continuous exposure to low PI concentrations, although pharmacokinetic analysis in patients has shown that serum concentrations of PIs change in a pulsatile manner. In the present study, we explored the effects of pulsatile treatment with PIs on bone metabolism to simulate in vivo PI pharmacokinetics. Pulsatile treatment with bortezomib, carfilzomib, or ixazomib induced MM cell death but only marginally affected the viability of osteoclasts (OCs) with F-actin ring formation. Pulsatile PI treatment suppressed osteoclastogenesis in OC precursors and bone resorption by mature OCs. OCs robustly enhanced osteoblastogenesis in cocultures with OCs and MC3T3-E1 pre-osteoblastic cells, indicating OC-mediated coupling to osteoblastogenesis. Importantly, pulsatile PI treatment did not impair robust OC-mediated osteoblastogenesis. These results suggest that PIs might sufficiently reduce MM cell-derived osteoblastogenesis inhibitors to permit OC-driven bone formation coupling while suppressing OC differentiation and activity in good responders to PIs. OC-mediated coupling to osteoblastogenesis appears to be a predominant mechanism for preferential occurrence of bone regeneration at sites of osteoclastic bone destruction in good responders. (Tokushima University Institutional Repository) ● Metadata: 118380 (Link to Publication Site) ● Publication site (DOI): 10.1007/s12185-023-03601-2 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37039914 ● Search Scopus @ Elsevier (PMID): 37039914 ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-023-03601-2 (Tokushima University Institutional Repository: 118380, DOI: 10.1007/s12185-023-03601-2, PubMed: 37039914)
11.	Takeshi Harada, Hiroto Ohguchi, Asuka Oda, Michiyasu Nakao, Jumpei Teramachi, Masahiro Hiasa, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Tomoko Maruhashi, Mamiko Takahashi, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Shuji Ozaki, Shigeki Sano, Teru Hideshima and Masahiro Abe : Novel antimyeloma therapeutic option with inhibition of the HDAC1-IRF4 axis and PIM kinase, Blood Advances, Vol.7, No.6, 1019-1032, 2023. (Summary) Multiple myeloma (MM) preferentially expands and acquires drug resistance in the bone marrow (BM). We herein examined the role of histone deacetylase 1 (HDAC1) in the constitutive activation of the master transcription factor IRF4 and the prosurvival mediator PIM2 kinase in MM cells. The knockdown or inhibition of HDAC1 by the class I HDAC inhibitor MS-275 reduced the basal expression of IRF4 and PIM2 in MM cells. Mechanistically, the inhibition of HDAC1 decreased IRF4 transcription through histone hyperacetylation and inhibiting the recruitment of RNA polymerase II at the IRF4 locus, thereby reducing IRF4-targeting genes, including PIM2. In addition to the transcriptional regulation of PIM2 by the HDAC1-IRF4 axis, PIM2 was markedly upregulated by external stimuli from BM stromal cells and interleukin-6 (IL-6). Upregulated PIM2 contributed to the attenuation of the cytotoxic effects of MS-275. Class I HDAC and PIM kinase inhibitors cooperatively suppressed MM cell growth in the presence of IL-6 and in vivo. Therefore, the present results demonstrate the potential of the simultaneous targeting of the intrinsic HDAC1-IRF4 axis plus externally activated PIM2 as an efficient therapeutic option for MM fostered in the BM. (Keyword) Histone Deacetylase 1 / Interleukin-6 / Benzamides / Pyridines (Tokushima University Institutional Repository) ● Metadata: 118211 (Link to Publication Site) ● Publication site (DOI): 10.1182/bloodadvances.2022007155 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36129197 ● Search Scopus @ Elsevier (PMID): 36129197 ● Search Scopus @ Elsevier (DOI): 10.1182/bloodadvances.2022007155 (Tokushima University Institutional Repository: 118211, DOI: 10.1182/bloodadvances.2022007155, PubMed: 36129197)
12.	Taiki Hori, Shingen Nakamura, Hiroki Yamagami, Saya Yasui, Minae Hosoki, Tomoyo Hara, Yukari Mitsui, Shiho Masuda, Kiyoe Kurahashi, Sumiko Yoshida, Takeshi Harada, Akio Kuroda, Toshiki Otoda, Tomoyuki Yuasa, Itsuro Endo, Munehide Matsuhisa, Masahiro Abe and Ken-ichi Aihara : Phase angle and extracellular water-to-total body water ratio estimated by bioelectrical impedance analysis are associated with levels of hemoglobin and hematocrit in patients with diabetes., Heliyon, Vol.9, No.4, 2023. (Summary) PhA and ECW/TBW but not SMI were associated with levels of Hgb and Hct in patients with diabetes. Therefore, aberrant values of PhA and ECW/TBW suggest a risk of anemia in diabetic patients. (Tokushima University Institutional Repository) ● Metadata: 118251 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.heliyon.2023.e14724 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37057050 ● Search Scopus @ Elsevier (PMID): 37057050 ● Search Scopus @ Elsevier (DOI): 10.1016/j.heliyon.2023.e14724 (Tokushima University Institutional Repository: 118251, DOI: 10.1016/j.heliyon.2023.e14724, PubMed: 37057050)
13.	Jumpei Teramachi, Hirokazu Miki, Shingen Nakamura, Masahiro Hiasa, Takeshi Harada and Masahiro Abe : Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents., Journal of Bone and Mineral Metabolism, 1-16, 2023. (Summary) MM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis and suppress osteoblastic differentiation from bone marrow stromal cells, leading to extensive bone destruction with rapid loss of bone. MM cells alter the microenvironment through bone destruction where they colonize, which in turn favors tumor growth and survival, thereby forming a vicious cycle between tumor progression and bone destruction. Denosumab or zoledronic acid is currently recommended to be administered at the start of treatment in newly diagnosed patients with MM with bone disease. Proteasome inhibitors and the anti-CD38 monoclonal antibody daratumumab have been demonstrated to exert bone-modifying activity in responders. Besides their anti-tumor activity, the effects of new anti-MM agents on bone metabolism should be more precisely analyzed in patients with MM. Because prognosis in patients with MM has been significantly improved owing to the implementation of new agents, the therapeutic impact of bone-modifying agents should be re-estimated in the era of these new agents. (Link to Publication Site) ● Publication site (DOI): 10.1007/s00774-023-01403-4 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36856824 ● Search Scopus @ Elsevier (PMID): 36856824 ● Search Scopus @ Elsevier (DOI): 10.1007/s00774-023-01403-4 (DOI: 10.1007/s00774-023-01403-4, PubMed: 36856824)
14.	Yoshiki Higa, Masahiro Hiasa, Hirofumi Tenshin, Emiko Nakaue, Mariko Tanaka, Sooha Kim, Motosumi Nakagawa, Sou Shimizu, Kotaro Tanimoto, Jumpei Teramachi, Takeshi Harada, Asuka Oda, Masahiro Oura, Kimiko Sogabe, Tomoyo Hara, Ryohei Sumitani, Tomoko Maruhashi, Hiroki Yamagami, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2., Antioxidants, Vol.12, No.1, 2023. (Summary) Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating. (Tokushima University Institutional Repository) ● Metadata: 118313 (Link to Publication Site) ● Publication site (DOI): 10.3390/antiox12010133 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36670994 ● Search Scopus @ Elsevier (PMID): 36670994 ● Search Scopus @ Elsevier (DOI): 10.3390/antiox12010133 (Tokushima University Institutional Repository: 118313, DOI: 10.3390/antiox12010133, PubMed: 36670994)
15.	高原由実子, Hirokazu Miki, Shingen Nakamura, 林成樹, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, 丸橋朋子, 富永誠記, 岡本秀樹, Naoto Okada, 矢野由美子, 高橋真理, 大坂朱美, Takeshi Harada, Shiroh Fujii, Toshiyuki Suge, Keiko Aota, Shuji Ozaki and Masahiro Abe : 徳島県におけるHIV感染症および後天性免疫不全症候群患者の臨床的特徴と今後の課題, Shikoku Acta Medica, Vol.78, No.5-6, 193-198, 2022. (Summary) 【Introduction】The survival rate in patients with HIV infection and acquired immunodeficiency syndrome (AIDS) has been improved dramatically due to the advances in anti-HIV drug therapy, while aging-associated complications become a critical issue. The incidence of sudden occurrence of AIDS without prior detection of HIV infection, so called ``Ikinari AIDS'', still remains high. 【Objective】We retrospectively analyzed the incidence and clinical characteristics of HIV/AIDS patients in both Tokushima University Hospital and Tokushima Prefectural Central Hospital. 【Results】Eighty four patients (74 males and 10 females) with a median age of 39 years old (range 16 - 85) were enrolled. Thirty-four patients (40.5%) were diagnosed with ``Ikinari AIDS'' from 2001 to 2020. All 4 patients were diagnosed with ``Ikinari AIDS'' after 2020. AIDS-defining illnesses were diagnosed as follows ; pneumocystis pneumonia in 21 cases, CMV infection in 8 cases and candidiasis in 6 cases. All patients over 60 years old were suffered from AIDS. Other complications included syphilis in 17 cases, hepatitis B infection in 12 and herpes zoster in 7. 【Discussion/Conclusion】In Tokushima, the incidence rate of ``Ikinari AIDS'' appeared to be higher than that of national average. COVID - 19 pandemic hampered the public health care services of awareness-raising activity for HIV infection and telephone consultations about HIV, which may become more lease asymptomatic HIV patients without diagnosis. For early diagnosis of HIV/AIDS, it is becoming more important to share information to make early screening of HIV infection among medical staffs, such as medical doctors, dentists, nurses, pharmacists and MSWs. (Keyword) HIV / AIDS / Ikinari AIDS (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520013962706680448 (CiNii: 1520013962706680448)
16.	Sou Shimizu, Jumpei Teramachi, Takeshi Harada, Masahiro Hiasa, Hirofumi Tenshin, A Oda, A Seki, Y Inoue, Kotaro Tanimoto, Yoshiki Higa, M Oura, K Sogabe, Takeshi Harada, Ryohei Sumitani, T Maruhashi, H Yamagami, Y Sawa, Itsuro Endo, K Tsuneyama, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : Aberrant upregulation of the endogenous PP2A inhibitor CIP2A is vital for myeloma cell growth and survival, International Journal of Myeloma, Vol.12, No.2, 14-23, 2022. (Summary) <p>The serine/threonine kinase TAK1 is constitutively overexpressed and auto-phosphorylated in multiple myeloma (MM) cells. Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which dephosphorylates proteins phosphorylated by various serine/threonine kinases to regulate multiple cellular functions. We recently reported that the serine/threonine kinase TGF-β-activated kinase-1 (TAK1) is highly expressed and auto-phosphorylated to mediate critical growth and survival signaling in MM cells. We demonstrate here that regulation of PP2A activity inversely affects the phosphorylation levels of TAK1 in MM cells, and that MM cells aberrantly overexpress cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor for PP2A. <i>CIP2A</i> gene silencing as well as treatment with the CIP2A inhibitor TD52 potently induced MM cell death along with suppression of TAK1 expression in MM cells. These results suggest the critical role of PP2A inactivation via CIP2A upregulation in TAK1 phosphorylation and its protein expression and thereby MM cell growth and survival, posing the CIP2A-PP2A axis as an important therapeutic target.</p> (Keyword) multiple myeloma / TAK1 / CIP2A / PP2A (Tokushima University Institutional Repository) ● Metadata: 117150 (Link to Publication Site) ● Publication site (DOI): 10.57352/ijm.12.2_14 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390573947533793024 ● Search Scopus @ Elsevier (DOI): 10.57352/ijm.12.2_14 (Tokushima University Institutional Repository: 117150, DOI: 10.57352/ijm.12.2_14, CiNii: 1390573947533793024)
17.	Kotaro Tanimoto, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Asuka Oda, Takeshi Harada, Yoshiki Higa, Kimiko Sogabe, Masahiro Oura, Ryohei Sumitani, Tomoyo Hara, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : Mechanical unloading aggravates bone destruction and tumor expansion in myeloma., Haematologica, Vol.107, No.3, 744-749, 2022. (Keyword) Bone Resorption / Humans / Multiple Myeloma / Osteoclasts / Osteolysis (Tokushima University Institutional Repository) ● Metadata: 116715 (Link to Publication Site) ● Publication site (DOI): 10.3324/haematol.2021.278295 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34788982 ● Search Scopus @ Elsevier (PMID): 34788982 ● Search Scopus @ Elsevier (DOI): 10.3324/haematol.2021.278295 (Tokushima University Institutional Repository: 116715, DOI: 10.3324/haematol.2021.278295, PubMed: 34788982)
18.	Hirofumi Tenshin, Jumpei Teramachi, Mohannad Ashtar, Masahiro Hiasa, Yusuke Inoue, Asuka Oda, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Tomoyo Hara, Ryohei Sumitani, Tomoko Maruhashi, Mayu Sebe, Rie Tsutsumi, Hiroshi Sakaue, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : TGF-β-activated kinase-1 inhibitor LL-Z1640-2 reduces joint inflammation and bone destruction in mouse models of rheumatoid arthritis by inhibiting NLRP3 inflammasome, TACE, TNF-α and RANKL expression., Clinical & translational immunology, Vol.11, No.1, 2022. (Summary) TAK1 inhibition with LLZ may become a novel treatment strategy to effectively alleviate inflammasome-mediated inflammation and RANKL-induced osteoclastic bone destruction in joints alongside its potent suppression of TNF-α and IL-6 production and proteinase-mediated pathological processes in RA. (Tokushima University Institutional Repository) ● Metadata: 117260 (Link to Publication Site) ● Publication site (DOI): 10.1002/cti2.1371 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35079379 ● Search Scopus @ Elsevier (PMID): 35079379 ● Search Scopus @ Elsevier (DOI): 10.1002/cti2.1371 (Tokushima University Institutional Repository: 117260, DOI: 10.1002/cti2.1371, PubMed: 35079379)
19.	Shin Kondo, Kumiko Kagawa, Takashi Saito, Masahiro Oura, Kimiko Sogabe, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Nori Sato, Rei Ono, Masahiro Abe and Shinsuke Katoh : Allogeneic haematopoietic stem cell transplantation-clinical outcomes: impact of leg muscle strength., BMJ Supportive & Palliative Care, 2021. (Summary) Pre-transplant LEMS was a significant factor in predicting OS and NRM. (Link to Publication Site) ● Publication site (DOI): 10.1136/bmjspcare-2021-003256 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34949601 ● Search Scopus @ Elsevier (PMID): 34949601 ● Search Scopus @ Elsevier (DOI): 10.1136/bmjspcare-2021-003256 (DOI: 10.1136/bmjspcare-2021-003256, PubMed: 34949601)
20.	Masahiro Hiasa, Takeshi Harada, Eiji Tanaka and Masahiro Abe : Pathogenesis and treatment of multiple myeloma bone disease., Japanese Dental Science Review, Vol.57, 164-173, 2021. (Summary) Multiple myeloma (Plasma cell myeloma), a malignancy of the plasma cells, exhibits tumor expansion preferentially in the bone marrow and the development of bone-destructive lesions. Multiple myeloma is still an incurable disease with changes in the bone marrow microenvironment in favor of the survival and proliferation of multiple myeloma cells and bone destruction. In this review, we described the recent findings on the regulators involved in the development of myeloma bone diseases, and succinctly summarize currently available therapeutic options and the development of novel bone modifying agents for myeloma treatment. (Tokushima University Institutional Repository) ● Metadata: 117254 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jdsr.2021.08.006 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34611468 ● Search Scopus @ Elsevier (PMID): 34611468 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jdsr.2021.08.006 (Tokushima University Institutional Repository: 117254, DOI: 10.1016/j.jdsr.2021.08.006, PubMed: 34611468)
21.	Atsushi Nakayama, Tenta Nakamura, Tabassum Ara, tatsuya fukuta, Sangita Karanjit, Takeshi Harada, Asuka Oda, Hideo Sato, Masahiro Abe, Kentaro Kogure and Kosuke Namba : Development of a novel antioxidant based on a dimeric dihydroisocoumarin derivative, Tetrahedron Letters, Vol.74, 153176, 2021. (Tokushima University Institutional Repository) ● Metadata: 116179 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.tetlet.2021.153176 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85107022552 (Tokushima University Institutional Repository: 116179, DOI: 10.1016/j.tetlet.2021.153176, Elsevier: Scopus)
22.	Jumpei Teramachi, Hirofumi Tenshin, Masahiro Hiasa, Asuka Oda, Ariunzaya Bat-Erdene, Takeshi Harada, Shingen Nakamura, Mohannad Ashtar, Sou Shimizu, Masami Iwasa, Kimiko Sogabe, Masahiro Oura, Shiroh Fujii, Kumiko Kagawa, Hirokazu Miki, Itsuro Endo, Tatsuji Haneji, Toshio Matsumoto and Masahiro Abe : TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma, Haematologica, Vol.106, No.5, 1401-1413, 2021. (Summary) Along with the tumor progression, the bone marrow microenvironment is skewed in multiple myeloma (MM), which underlies the unique pathophysiology of MM and confers aggressiveness and drug resistance in MM cells. TGF-β-activated kinase-1 (TAK1) mediates a wide range of intracellular signaling pathways. We demonstrate here that TAK1 is constitutively overexpressed and phosphorylated in MM cells, and that TAK1 inhibition suppresses the activation of NF-κB, p38MAPK, ERK and STAT3 to decrease the expression of critical mediators for MM growth and survival, including PIM2, MYC, Mcl-1, IRF4, and Sp1, along with a substantial reduction in the angiogenic factor VEGF in MM cells. Intriguingly, TAK1 phosphorylation was also induced along with upregulation of vascular cell adhesion molecule-1 (VCAM-1) in bone marrow stromal cells (BMSCs) in cocultures with MM cells, which facilitated MM cell-BMSC adhesion while inducing IL-6 production and receptor activator of nuclear factor κ-Β ligand (RANKL) expression by BMSCs. TAK1 inhibition effectively impaired MM cell adhesion to BMSCs to disrupt the support of MM cell growth and survival by BMSCs. Furthermore, TAK1 inhibition suppressed osteoclastogenesis enhanced by RANKL in cocultures of bone marrow cells with MM cells, and restored osteoblastic differentiation suppressed by MM cells or inhibitory factors for osteoblastogenesis overproduced in MM. Finally, treatment with the TAK1 inhibitor LLZ1640-2 markedly suppressed MM tumor growth and prevented bone destruction and loss in mouse MM models. Therefore, TAK1 inhibition may be a promising therapeutic option targeting not only MM cells but also the skewed bone marrow microenvironment in MM. (Keyword) Animals / Bone Marrow Cells / MAP Kinase Kinase Kinases / Mice / Multiple Myeloma / NF-kappa B / Osteoclasts / Osteolysis / RANK Ligand / Tumor Microenvironment (Tokushima University Institutional Repository) ● Metadata: 116529 (Link to Publication Site) ● Publication site (DOI): 10.3324/haematol.2019.234476 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32273474 ● Search Scopus @ Elsevier (PMID): 32273474 ● Search Scopus @ Elsevier (DOI): 10.3324/haematol.2019.234476 (Tokushima University Institutional Repository: 116529, DOI: 10.3324/haematol.2019.234476, PubMed: 32273474)
23.	Ryohei Sumitani, Taiki Hori, Jumpei Murai, Shiyori Kawata, Masahiro Oura, Kimiko Sogabe, Mamiko Takahashi, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Masahiro Abe and Shingen Nakamura : Acute Myeloid Leukemia Developing with Acute Pancreatitis Mimicking Autoimmune Pancreatitis., Internal Medicine, Vol.60, No.11, 1753-1757, 2021. (Summary) A 33-year-old man was admitted to our hospital for fever and abdominal pain. A blood analysis revealed pancytopenia and increased serum pancreatic enzymes with disseminated intravascular coagulation. A detailed examination revealed acute pancreatitis, with diffuse swelling of the pancreas and diffuse beaded dilatation of the main pancreatic duct, which mimicked autoimmune pancreatitis complicated by acute myeloid leukemia. Systemic cytotoxic chemotherapy led to the remission of leukemia and pancreatitis. We hypothesized that the etiology of acute pancreatitis was invasion of leukemia cells. Acute pancreatitis is rare as a symptom of leukemia; however, we should consider the possibility of leukemia during the differential diagnosis of acute pancreatitis. (Keyword) Acute Disease / Adult / Autoimmune Diseases / Autoimmune Pancreatitis / Humans / Leukemia, Myeloid, Acute / Male / Pancreatitis (Tokushima University Institutional Repository) ● Metadata: 116536 (Link to Publication Site) ● Publication site (DOI): 10.2169/internalmedicine.4916-20 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33456032 ● Search Scopus @ Elsevier (PMID): 33456032 ● Search Scopus @ Elsevier (DOI): 10.2169/internalmedicine.4916-20 (Tokushima University Institutional Repository: 116536, DOI: 10.2169/internalmedicine.4916-20, PubMed: 33456032)
24.	Teru Hideshima, Daisuke Ogiya, Jiye Liu, Takeshi Harada, Keiji Kurata, Jooeun Bae, Walter Massefski and Kenneth Anderson : Immunomodulatory drugs activate NK cells via both Zap-70 and cereblon-dependent pathways, Leukemia, Vol.35, No.1, 177-188, 2021. (Summary) Immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide show remarkable antitumor activity in multiple myeloma (MM) via directly inhibiting MM-cell growth in the bone marrow (BM) microenvironment and promoting immune effector cell function. They are known to bind to the ubiquitin 3 ligase CRBN complex and thereby triggering degradation of IKZF1/3. In this study, we demonstrate that IMiDs also directly bind and activate zeta-chain-associated protein kinase-70 (Zap-70) via its tyrosine residue phosphorylation in T cells. IMiDs also triggered phosphorylation of Zap-70 in natural killer (NK) cells. Importantly, increased granzyme-B (GZM-B) expression and NK-cell activity triggered by IMiDs is associated with Zap-70 activation and inhibited by Zap-70 knockdown (KD), independent of CRBN. We also demonstrate a second mechanism whereby IMiDs trigger GZM-B and NK cytotoxicity which is CRBN and IKZF3 mediated, and inhibited or enhanced by KD of CRBN or IKZF3, respectively, independent of Zap-70. Our studies therefore show that IMiDs can enhance NK and T-cell cytotoxicity in (1) ZAP-70-mediated CRBN independent, as well as (2) CRBN-mediated ZAP-70 independent mechanisms; and provide the framework for developing novel therapeutics to activate Zap-70 and thereby enhance T and NK anti-MM cytotoxicity. (Keyword) Adaptor Proteins, Signal Transducing / Cell Line, Tumor / Cells, Cultured / Cytotoxicity, Immunologic / Humans / Immunologic Factors / Immunomodulation / Killer Cells, Natural / Lymphocyte Activation / Phosphorylation / Signal Transduction / T-Lymphocyte Subsets / Ubiquitin-Protein Ligases / ZAP-70 Protein-Tyrosine Kinase (Link to Publication Site) ● Publication site (DOI): 10.1038/s41375-020-0809-x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32238854 ● Summary page in Scopus @ Elsevier: 2-s2.0-85082750526 (DOI: 10.1038/s41375-020-0809-x, PubMed: 32238854, Elsevier: Scopus)
25.	Mamiko Takahashi, Ryohei Sumitani, Taiki Hori, Jumpei Murai, Shiyori Kawata, Masahiro Oura, Kimiko Sogabe, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Masahiro Abe and Shingen Nakamura : Intravenous busulfan-based conditioning with autologous stem cell transplantation for refractory B-cell lymphoma with central nervous system involvement., The Journal of Medical Investigation : JMI, Vol.68, No.1.2, 196-201, 2021. (Summary) The prognosis of relapsed or refractory lymphoma with central nervous system (CNS) involvement remains poor because of the lack of anticancer drugs with sufficient CNS penetration. [Case 1] A 65-year-old man was diagnosed with Stage IV mantle cell lymphoma. After two courses of chemotherapy and autologous hematopoietic stem cell (HSC) collection, urinary retention with fever developed. Cerebrospinal fluid analysis revealed leptomeningeal involvement, which was refractory to high-dose methotrexate therapy. Autologous peripheral blood stem cell transplantation (ASCT) was performed, followed by intravenous busulfan (ivBU), cyclophosphamide, and etoposide ; thereafter, no relapse has been detected for over six years. [Case 2] A 40-year-old woman with right lower hemiplegia was diagnosed with primary CNS lymphoma. Although four courses of high-dose methotrexate therapy were administered, the cerebral tumor increased in size. HSCs were collected after methotrexate therapy, and ASCT was performed in addition to conditioning using ivBU, cyclophosphamide, and etoposide, followed by whole-brain and local boost irradiation. She achieved complete remission, but relapsed two years after ASCT. High-dose ivBU-containing conditioning regimens with ASCT may be useful for refractory B-cell lymphoma with CNS involvement. J. Med. Invest. 68 : 196-201, February, 2021. (Tokushima University Institutional Repository) ● Metadata: 116021 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.68.196 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33994471 ● Search Scopus @ Elsevier (PMID): 33994471 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.68.196 (Tokushima University Institutional Repository: 116021, DOI: 10.2152/jmi.68.196, PubMed: 33994471)
26.	Mohannad Ashtar, Hirofumi Tenshin, Jumpei Teramachi, Ariunzaya Bat-Erdene, Masahiro Hiasa, Asuka Oda, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Shingen Nakamura, Shiroh Fujii, Ryohei Sumitani, Hirokazu Miki, Kengo Udaka, Mamiko Takahashi, Kumiko Kagawa, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat., Cancers, Vol.12, No.4, 2020. (Summary) Receptor activator of NF-κB ligand (RANKL), a critical mediator of osteoclastogenesis, is upregulated in multiple myeloma (MM). The xanthine oxidase inhibitor febuxostat, clinically used for prevention of tumor lysis syndrome, has been demonstrated to effectively inhibit not only the generation of uric acid but also the formation of reactive oxygen species (ROS). ROS has been demonstrated to mediate RANKL-mediated osteoclastogenesis. In the present study, we therefore explored the role of cancer-treatment-induced ROS in RANKL-mediated osteoclastogenesis and the suppressive effects of febuxostat on ROS generation and osteoclastogenesis. RANKL dose-dependently induced ROS production in RAW264.7 preosteoclastic cells; however, febuxostat inhibited the RANKL-induced ROS production and osteoclast (OC) formation. Interestingly, doxorubicin (Dox) further enhanced RANKL-induced osteoclastogenesis through upregulation of ROS production, which was mostly abolished by addition of febuxostat. Febuxostat also inhibited osteoclastogenesis enhanced in cocultures of bone marrow cells with MM cells. Importantly, febuxostat rather suppressed MM cell viability and did not compromise Dox's anti-MM activity. In addition, febuxostat was able to alleviate pathological osteoclastic activity and bone loss in ovariectomized mice. Collectively, these results suggest that excessive ROS production by aberrant RANKL overexpression and/or anticancer treatment disadvantageously impacts bone, and that febuxostat can prevent the ROS-mediated osteoclastic bone damage. (Tokushima University Institutional Repository) ● Metadata: 115041 (Link to Publication Site) ● Publication site (DOI): 10.3390/cancers12040929 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32283857 ● Search Scopus @ Elsevier (PMID): 32283857 ● Search Scopus @ Elsevier (DOI): 10.3390/cancers12040929 (Tokushima University Institutional Repository: 115041, DOI: 10.3390/cancers12040929, PubMed: 32283857)
27.	Kengo Udaka, Shingen Nakamura, Shiroh Fujii, Ryosuke Miyamoto, Naoko Matsui, Shiyori Kawata, Taiki Hori, Junpei Murai, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Mamiko Takahashi, Takeshi Harada, Kumiko Kagawa, Yuishin Izumi, Masahiro Abe and Hirokazu Miki : Successful treatment of progressive multifocal leukoencephalopathy with mirtazapine and mefloquine in refractory myeloma, International Journal of Myeloma, Vol.10, No.1, 8-12, 2020.
28.	Matthew Ho, Tianzeng Chen, Jiye Liu, Paul Dowling, Teru Hideshima, Li Zhang, Eugenio Morelli, Gulden Camci-Unal, Xinchen Wu, Yu-Tzu Tai, Kenneth Wen, Mehmet Samur, Robert L. Schlossman, Ralph Mazitschek, Emma L. Kavanagh, Sinead Lindsay, Takeshi Harada, Amanda McCann, Kenneth C. Anderson, Peter O'Gorman and Giada Bianchi : Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling, Leukemia, Vol.34, No.1, 196-209, 2020. (Tokushima University Institutional Repository) ● Metadata: 115638 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41375-019-0493-x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31142847 ● Summary page in Scopus @ Elsevier: 2-s2.0-85066789015 (Tokushima University Institutional Repository: 115638, DOI: 10.1038/s41375-019-0493-x, PubMed: 31142847, Elsevier: Scopus)
29.	Shuji Ozaki, Takeshi Harada, Hikaru Yagi, Etsuko Sekimoto, Hironobu Shibata, Toshio Shigekiyo, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa and Masahiro Abe : Polyclonal Immunoglobulin Recovery after Autologous Stem Cell Transplantation Is an Independent Prognostic Factor for Survival Outcome in Patients with Multiple Myeloma, Cancers, Vol.12, No.1, 12, 2019. (Summary) We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in ≥complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, 46.8 vs 26.7 months, = 0.0071) and overall survival (OS, median, not reached vs 65.3 months, < 0.00001) compared with those without Ig recovery. The survival benefits of Ig recovery were similarly observed in ≥CR patients (median OS, not reached vs 80.5 months, = 0.061) and non-CR patients (median OS, not reached vs 53.2 months, = 0.00016). Multivariate analysis revealed that non-CR and not all Ig recovery were independent prognostic factors for PFS (HR, 4.284, 95%CI (1.868-9.826), = 0.00059; and HR, 2.804, 95%CI (1.334-5.896), = 0.0065, respectively) and also for OS (HR, 8.245, 95%CI (1.528-44.47), = 0.014; and HR, 36.55, 95%CI (3.942-338.8), = 0.0015, respectively). Therefore, in addition to the depth of response, the recovery of polyclonal Ig after ASCT is a useful indicator especially for long-term outcome and might be considered to prevent overtreatment with maintenance therapy in transplanted patients with MM. (Tokushima University Institutional Repository) ● Metadata: 115047 (Link to Publication Site) ● Publication site (DOI): 10.3390/cancers12010012 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31861479 ● Summary page in Scopus @ Elsevier: 2-s2.0-85077198248 (Tokushima University Institutional Repository: 115047, DOI: 10.3390/cancers12010012, PubMed: 31861479, Elsevier: Scopus)
30.	Masami Iwasa, Takeshi Harada, Asuka Oda, Ariunzaya Bat-Erdene, Jumpei Teramachi, Hirofumi Tenshin, Mohannad Ashtar, Masahiro Oura, Kimiko Sogabe, Kengo Udaka, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Shuji Ozaki and Masahiro Abe : PD-L1 upregulation in myeloma cells by panobinostat in combination with interferon-γ., Oncotarget, Vol.10, No.20, 1903-1917, 2019. (Summary) gene silencing abolished the PD-L1 upregulation by panobinostat and IFN-γ in combination, indicating a critical role for STAT1. These results suggest that panobinostat enhances PD-L1 expression by facilitating the IFN-γ-STAT1 pathway in a ligand-dependent manner in MM cells with ambient IFN-γ. PD-L1 upregulation should be taken into account when combining immunotherapies with panobinostat. (Tokushima University Institutional Repository) ● Metadata: 113359 (Link to Publication Site) ● Publication site (DOI): 10.18632/oncotarget.26726 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30956773 ● Summary page in Scopus @ Elsevier: 2-s2.0-85062760316 (Tokushima University Institutional Repository: 113359, DOI: 10.18632/oncotarget.26726, PubMed: 30956773, Elsevier: Scopus)
31.	Yuko Miyakami, Shingen Nakamura, Masahiro Oura, Yasunobu Okamoto, 高橋真美子, Kimiko Sogabe, 岩佐昌美, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Hisanori Uehara and Masahiro Abe : De novo CD 20-negative diffuse large B-cell lymphoma developed with sustained fever and markedly high C-reactive protein level, Shikoku Acta Medica, Vol.74, No.5-6, 193-200, 2018. (Summary) A 68-year-old woman presented with sustained fever for more than 1 month and admitted due to hematemesis and systemic edema. Computed tomography scan revealed swelling of the cervical, paraaortic lymph nodes. Blood test results showed severe anemia, elevation of white blood cell count, elevation of liver enzyme and coagulopathy with high C-reactive protein. Biopsy of the right cervical lymph node showed proliferation of abnormal lymphoid cells with necrosis and hemorrhage, which are positive for CD79α, CD30, MUM-1, and bcl-6 and negative for CD20, CD5, CD10, ALK, CD38, CD138, and EBER. Gene rearrangement of immunoglobulin heavy chain was detected in tumor cells. Bone marrow aspiration showed tumor involvement. The patient was diagnosed with de novo CD20-negative diffuse large B-cell lymphoma(DLBCL)stage IV B. Reduced CHOP therapy was performed under artificial respiration due to pulmonary edema and takotsubo cardiomyopathy. Although her general condition and high CRP levels temporarily improved, she died 47 days after admission due to rapid relapse. De novo CD20-negative DLBCL was rare and presented with high CRP levels and rapid progression, and was thought to be clinically different from the existing DLBCL. It is imperative to elucidate molecular pathophysiology and establish new treatment strategy for de novo CD20-negative DLBCL. (Keyword) CD20 / fever of unknown origin / diffuse large B-cell lymphoma / CRP (Tokushima University Institutional Repository) ● Metadata: 112987 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050583647829887360 (Tokushima University Institutional Repository: 112987, CiNii: 1050583647829887360)
32.	Ariunzaya Bat-Erdene, Shingen Nakamura, Asuka Oda, Masami Iwasa, Jumpei Teramachi, Mohannad Ashtar, Takeshi Harada, Hirokazu Miki, Hirofumi Tenshin, Masahiro Hiasa, Shiroh Fujii, Kimiko Sogabe, Masahiro Oura, Kengo Udaka, Kumiko Kagawa, Sumiko Yoshida, Ken-ichi Aihara, Kiyoe Kurahashi, Itsuro Endo and Masahiro Abe : Class 1 HDAC and HDAC6 inhibition inversely regulates CD38 induction in myeloma cells via interferon-α and ATRA., British Journal of Haematology, 2018. (Tokushima University Institutional Repository) ● Metadata: 113393 (Link to Publication Site) ● Publication site (DOI): 10.1111/bjh.15673 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30474853 ● Summary page in Scopus @ Elsevier: 2-s2.0-85057280798 (Tokushima University Institutional Repository: 113393, DOI: 10.1111/bjh.15673, PubMed: 30474853, Elsevier: Scopus)
33.	Anamaria Gulla, Teru Hideshima, Giada Bianchi, MT Fulciniti, M Samur Kemal, J Qi, Yu-Tzu Tai, Takeshi Harada, E Morelli, N Amodio, R Carrasco, P Tagliaferri, NC Munshi, P Tassone and C. Kenneth Anderson : Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma, Leukemia, Vol.32, No.4, 996-1002, 2018. (Summary) Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-κB signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-κB inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome. (Link to Publication Site) ● Publication site (DOI): 10.1038/leu.2017.334 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29158558 ● Summary page in Scopus @ Elsevier: 2-s2.0-85044660056 (DOI: 10.1038/leu.2017.334, PubMed: 29158558, Elsevier: Scopus)
34.	Shiroh Fujii, Shingen Nakamura, Asuka Oda, Hirokazu Miki, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Itsuro Endo, Sumiko Yoshida, Ken-ichi Aihara, Kiyoe Kurahashi, Takeshi Harada, Kumiko Kagawa, Michiyasu Nakao, Shigeki Sano and Masahiro Abe : Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity., British Journal of Haematology, Vol.180, No.2, 246-258, 2018. (Summary) Proviral Integrations of Moloney virus 2 (PIM2) is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX-6258 and PIM447. SMI-16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations and reduced in vitro colony-forming capacity and in vivo tumourigenic activity in MM cells, suggesting impairment of their clonogenic capacity. PIM2 is known to be subject to ubiquitination-independent proteasomal degradation. Consistent with this, the proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in MM cells without affecting its mRNA levels. However, SMI-16a mitigated the PIM2 protein increase and cooperatively enhanced anti-MM effects in combination with carfilzomib. Collectively, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a uniquely reduce PIM2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned. (Keyword) Animals / Antineoplastic Agents / Cell Line, Tumor / Cell Survival / Cell Transformation, Neoplastic / Disease Models, Animal / Humans / Hydrogen-Ion Concentration / Mice / Multiple Myeloma / Proteasome Inhibitors / Protein-Serine-Threonine Kinases / Proteolysis / Proto-Oncogene Proteins / Thiazolidinediones (Tokushima University Institutional Repository) ● Metadata: 112752 (Link to Publication Site) ● Publication site (DOI): 10.1111/bjh.15033 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29327347 ● Summary page in Scopus @ Elsevier: 2-s2.0-85040344893 (Tokushima University Institutional Repository: 112752, DOI: 10.1111/bjh.15033, PubMed: 29327347, Elsevier: Scopus)
35.	山口純代, Shingen Nakamura, 住田智志, 前田悠作, Masahiro Oura, 高橋真美子, 岩佐昌美, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Jun Kishi and Masahiro Abe : Development of adult T-cell leukemia/lymphoma during immunosuppressive Therapy for human T-cell leukemia virus type 1 associated arthropathy, Shikoku Acta Medica, Vol.73, No.5,6, 301-308, 2017. (Summary) A 64-year-old woman presented with lower leg edema, fever, and bilateral joint pain, involving the wrists, fingers, and knees, in April 201X. Serological test results were negative for rheumatoid factor, antinuclear antibody, and anti-cyclic citrullinated peptide antibody. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema syndrome, a type of seronegative rheumatoid arthritis, was made and prednisolone was administered. The joint pain was refractory to prednisolone therapy. In February, 201X+2, the patient presented with right cervical lymphadenopathy. The CT scan revealed swelling of the cervical, axillary, and inguinal lymph nodes bilaterally and rapidly enlarged. In April, 18F-fluorodeoxyglucose PET/CT scan showed an abnormal collection in the enlarged lymph nodes. The patient subsequently developed hoarseness with dyspnea and attended our department. Blood test results showed high levels of lactate dehydrogenase (547U/L) and soluble interleukin‐2 receptor (34200 IU/L) and were positive for anti-human T-cell leukemia virus type1 (HTLV‐1) antibody. Biopsy of the right cervical lymph node showed proliferation of abnormal lymphoid cells positive for CD3, CD4, and CD25 and negative for CD7. Monoclonal integration of HTLV‐1 proviral DNA was detected in the lymph node. A diagnosis of adult T-cell leukemia/lymphoma (ATLL), lymphoma type was made. The pain involving multiple joints was attributed to HTLV‐1associated arthropathy. Immunosuppressive therapy for HTLV‐1 carrier status may have played a role in the development of ATLL. (Keyword) Adult T-cell leukemia/lymphoma / HTLV-1 / rheumatoid arthritis / immunosuppressive therapy (Tokushima University Institutional Repository) ● Metadata: 112059 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050020697876757248 (Tokushima University Institutional Repository: 112059, CiNii: 1050020697876757248)
36.	Hiroto Ohguchi, Takeshi Harada, Morihiko Sagawa, Shohei Kikuchi, YT Tai, PG Richardson, Teru Hideshima and KC Anderson : KDM6B modulates MAPK pathway mediating multiple myeloma cell growth and survival, Leukemia, Vol.31, No.12, 2661-2669, 2017. (Summary) Recent studies have delineated cancer-type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM) cells; and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. Tumor necrosis factor-α or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting that KDM6B is regulated by NF-κB signaling in MM cells. RNA-seq and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates expression of these genes without affecting H3K27 methylation level. Overexpression of catalytically inactive KDM6B activates expression of MAPK pathway-related genes, confirming its function independent of demethylase activity. We further demonstrate that downstream targets of KDM6B, ELK1 and FOS, confer MM cell growth. Our study therefore delineates KDM6B function that links NF-κB and MAPK signaling pathway mediating MM cell growth and survival, and validates KDM6B as a novel therapeutic target in MM. (Keyword) Cell Line, Tumor / Cell Proliferation / Cell Survival / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Humans / Jumonji Domain-Containing Histone Demethylases / MAP Kinase Signaling System / Multiple Myeloma / NF-kappa B / Proto-Oncogene Proteins c-fos / RNA Interference / Signal Transduction / ets-Domain Protein Elk-1 (Link to Publication Site) ● Publication site (DOI): 10.1038/leu.2017.141 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28487543 ● Summary page in Scopus @ Elsevier: 2-s2.0-85029548144 (DOI: 10.1038/leu.2017.141, PubMed: 28487543, Elsevier: Scopus)
37.	Takeshi Harada, Ohguchi Hiroto, Grondin Yohann, Kikuchi Shohei, Sagawa Morihiko, Tai Yu-Tzu, Mazitschek Ralph, Hideshima Teru and Anderson C. Kenneth : HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications, Leukemia, Vol.31, No.12, 2670-2677, 2017. (Summary) Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers, including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation. Here we show that knockdown of HDAC3, but not HDAC1 or HDAC2, as well as BG45, downregulate expression of DNA methyltransferase 1 (DNMT1) mediating MM cell proliferation. DNMT1 expression is regulated by c-Myc, and HDAC3 inhibition triggers degradation of c-Myc protein. Moreover, HDAC3 inhibition results in hyperacetylation of DNMT1, thereby reducing the stability of DNMT1 protein. Combined inhibition of HDAC3 and DNMT1 with BG45 and DNMT1 inhibitor 5-azacytidine (AZA), respectively, triggers synergistic downregulation of DNMT1, growth inhibition and apoptosis in both MM cell lines and patient MM cells. Efficacy of this combination treatment is confirmed in a murine xenograft MM model. Our results therefore provide the rationale for combination treatment using HDAC3 inhibitor with DNMT1 inhibitor to improve patient outcome in MM. (Keyword) Multiple myeloma / HDAC / DNMT1 (Link to Publication Site) ● Publication site (DOI): 10.1038/leu.2017.144 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28490812 ● Summary page in Scopus @ Elsevier: 2-s2.0-85035103653 (DOI: 10.1038/leu.2017.144, PubMed: 28490812, Elsevier: Scopus)
38.	Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiroh Fujii, Kiyoe Kurahashi, Sumiko Yoshida, Kumiko Kagawa, Itsuro Endo, Aihara Kenichi, Mariko Ikuo, Kouji Itou, Koichiro Hayashi, Michihiro Nakamura and Masahiro Abe : Effective impairment of myeloma cells and their progenitors by hyperthermia., Oncotarget, Vol.9, No.12, 10307-10316, 2017. (Summary) Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated "side population" fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs. (Tokushima University Institutional Repository) ● Metadata: 113059 (Link to Publication Site) ● Publication site (DOI): 10.18632/oncotarget.23121 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29535808 ● Summary page in Scopus @ Elsevier: 2-s2.0-85041952629 (Tokushima University Institutional Repository: 113059, DOI: 10.18632/oncotarget.23121, PubMed: 29535808, Elsevier: Scopus)
39.	Hirofumi Tenshin, Jumpei Teramachi, Asuka Oda, Ryota Amachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Keiichiro Watanabe, Masami Iwasa, Takeshi Harada, Shiroh Fujii, Kumiko Kagawa, Kimiko Sogabe, Shingen Nakamura, Hirokazu Miki, Kiyoe Kurahashi, Sumiko Yoshida, Kenichi Aihara, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects., Blood Advances, Vol.1, No.24, 2124-2137, 2017. (Summary) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) agonists induce tumor-specific apoptosis indicating that they may be an attractive therapeutic strategy against cancers, including multiple myeloma (MM). Osteoclastogenesis is highly induced in MM, which in turn enhances MM growth, thereby forming a vicious cycle between MM tumor expansion and bone destruction. However, the effects of TRAIL on MM-enhanced osteoclastogenesis remain largely unknown. Here, we show that TRAIL induced apoptosis in MM cells, but not in osteoclasts (OCs), and that it rather facilitated receptor activator of NF-B ligand-induced osteoclastogenesis along with upregulation of cellular FLICE inhibitory protein (c-FLIP). TRAIL did not induce death-inducing signaling complex formation in OCs, but formed secondary complex (complex II) with the phosphorylation of transforming growth factor -activated kinase-1 (TAK1), and thus activated NF-B signaling. c-FLIP knockdown abolished complex II formation, thus permitting TRAIL induction of OC cell death. The TAK1 inhibitor LLZ1640-2 abrogated the TRAIL-induced c-FLIP upregulation and NF-B activation, and triggered TRAIL-induced caspase-8 activation and cell death in OCs. Interestingly, the TRAIL-induced caspase-8 activation caused enzymatic degradation of the transcription factor Sp1 to noticeably reduce c-FLIP expression, which further sensitized OCs to TRAIL-induced apoptosis. Furthermore, the TAK1 inhibition induced antiosteoclastogenic activity by TRAIL even in cocultures with MM cells while potentiating TRAIL's anti-MM effects. These results demonstrated that osteoclastic lineage cells use TRAIL for their differentiation and activation through tilting caspase-8-dependent apoptosis toward NF-B activation, and that TAK1 inhibition subverts TRAIL-mediated NF-B activation to resume TRAIL-induced apoptosis in OCs while further enhancing MM cell death in combination with TRAIL. (Tokushima University Institutional Repository) ● Metadata: 111724 (Link to Publication Site) ● Publication site (DOI): 10.1182/bloodadvances.2017008813 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29296860 ● Search Scopus @ Elsevier (PMID): 29296860 ● Search Scopus @ Elsevier (DOI): 10.1182/bloodadvances.2017008813 (Tokushima University Institutional Repository: 111724, DOI: 10.1182/bloodadvances.2017008813, PubMed: 29296860)
40.	Morihiko Sagawa, Hiroto Ohguchi, Takeshi Harada, K. Mehmet Samur, Yu-Tzu Tai, C. Nikhil Munshi, Masahiro Kizaki, Teru Hideshima and C. Kenneth Anderson : Ribonucleotide Reductase Catalytic Subunit M1 (RRM1) as a Novel Therapeutic Target in Multiple Myeloma, Clinical Cancer Research, Vol.23, No.17, 5225-5237, 2017. (Summary) To investigate the biological and clinical significance of ribonucleotide reductase (RR) in multiple myeloma. We assessed the impact of RR expression on patient outcome in multiple myeloma. We then characterized the effect of genetic and pharmacologic inhibition of ribonucleotide reductase catalytic subunit M1 (RRM1) on multiple myeloma growth and survival using siRNA and clofarabine, respectively, in both and mouse xenograft models. Newly diagnosed multiple myeloma patients with higher RRM1 expression have shortened survival. Knockdown of RRM1 triggered significant growth inhibition and apoptosis in multiple myeloma cells, even in the context of the bone marrow microenvironment. Gene expression profiling showed upregulation of DNA damage response genes and p53-regulated genes after RRM1 knockdown. Immunoblot and qRT-PCR analysis confirmed that γ-H2A.X, ATM, ATR, Chk1, Chk2, RAD51, 53BP1, BRCA1, and BRCA2 were upregulated/activated. Moreover, immunoblots showed that p53, p21, Noxa, and Puma were activated in p53 wild-type multiple myeloma cells. Clofarabine, a purine nucleoside analogue that inhibits RRM1, induced growth arrest and apoptosis in p53 wild-type cell lines. Although clofarabine did not induce cell death in p53-mutant cells, it did trigger synergistic toxicity in combination with DNA-damaging agent melphalan. Finally, we demonstrated that tumor growth of RRM1-knockdown multiple myeloma cells was significantly reduced in a murine human multiple myeloma cell xenograft model. Our results therefore demonstrate that RRM1 is a novel therapeutic target in multiple myeloma in the preclinical setting and provide the basis for clinical evaluation of RRM1 inhibitor, alone or in combination with DNA-damaging agents, to improve patient outcome in multiple myeloma. . (Keyword) Animals / apoptosis / Biomarkers, Tumor / Cell Line, Tumor / Cell Survival / Gene Expression Regulation, Neoplastic / Humans / Mice / Molecular Targeted Therapy / Multiple Myeloma / Neoplasm Proteins / RNA, Small Interfering / Tumor Suppressor Proteins / Xenograft Model Antitumor Assays (Link to Publication Site) ● Publication site (DOI): 10.1158/1078-0432.CCR-17-0263 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28442502 ● Summary page in Scopus @ Elsevier: 2-s2.0-85029419578 (DOI: 10.1158/1078-0432.CCR-17-0263, PubMed: 28442502, Elsevier: Scopus)
41.	Ariunzaya Bat-Erdene, Hirokazu Miki, Asuko Oda, Shingen Nakamura, Jumpei Teramachi, Ryota Amachi, Hirofumi Tenshin, Masahiro Hiasa, Masami Iwasa, Takeshi Harada, Shiroh Fujii, Kimiko Sogabe, Kumiko Kagawa, Sumiko Yoshida, Itsuro Endo, Ken-ichi Aihara and Masahiro Abe : Synergistic targeting of Sp1, a critical transcription factor for myeloma cell growth and survival, by panobinostat and proteasome inhibitors., Oncotarget, Vol.7, No.48, 79064-79075, 2016. (Summary) Panobinostat, a pan-deacetylase inhibitor, synergistically elicits cytotoxic activity against myeloma (MM) cells in combination with the proteasome inhibitor bortezomib. Because precise mechanisms for panobinostat's anti-MM action still remain elusive, we aimed to clarify the mechanisms of anti-MM effects of panobinostat and its synergism with proteasome inhibitors. Although the transcription factor Sp1 was overexpressed in MM cells, the Sp1 inhibitor terameprocol induced MM cell death in parallel with reduction of IRF4 and cMyc. Panobinostat induced activation of caspase-8, which was inversely correlated with reduction of Sp1 protein levels in MM cells. The panobinostat-mediated effects were further potentiated to effectively induce MM cell death in combination with bortezomib or carfilzomib even at suboptimal concentrations as a single agent. Addition of the caspase-8 inhibitor z-IETD-FMK abolished the Sp1 reduction not only by panobinostat alone but also by its combination with bortezomib, suggesting caspase-8-mediated Sp1 degradation. The synergistic Sp1 reduction markedly suppressed Sp1-driven prosurvival factors, IRF4 and cMyc. Besides, the combinatory treatment reduced HDAC1, another Sp1 target, in MM cells, which may potentiate HDAC inhibition. Collectively, caspase-8-mediated post-translational Sp1 degradation appears to be among major mechanisms for synergistic anti-MM effects of panobinostat and proteasome inhibitors in combination. (Tokushima University Institutional Repository) ● Metadata: 109988 (Link to Publication Site) ● Publication site (DOI): 10.18632/oncotarget.12594 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27738323 ● Search Scopus @ Elsevier (PMID): 27738323 ● Search Scopus @ Elsevier (DOI): 10.18632/oncotarget.12594 (Tokushima University Institutional Repository: 109988, DOI: 10.18632/oncotarget.12594, PubMed: 27738323)
42.	Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E. Szalat, Paul G. Richardson, Nikhil C. Munshi, David M. Dorfman and Kenneth C. Anderson : A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications, Oncotarget, Vol.7, No.47, 77326-77341, 2016. (Summary) Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system. In the 3D model, MSC with conserved phenotype (CD73+CD90+CD105+) formed compact clusters with active fibrous connections, and retained lineage differentiation capacity. Extracellular matrix molecules, integrins, and niche related molecules including N-cadherin and CXCL12 are expressed in 3D MSC model. Furthermore, activation of osteogenesis (MMP13, SPP1, ADAMTS4, and MGP genes) and osteoblastogenic differentiation was confirmed in 3D MSC model. Co-culture of patient-derived BM mononuclear cells with either autologous or allogeneic MSC in 3D model increased proliferation of MM cells, CXCR4 expression, and SP cells. We carried out immune profiling to show that distribution of immune cell subsets was similar in 3D and 2D MSC model systems. Importantly, resistance to novel agents (IMiDs, bortezomib, carfilzomib) and conventional agents (doxorubicin, dexamethasone, melphalan) was observed in 3D MSC system, reflective of clinical resistance. This 3D MSC model may therefore allow for studies of MM pathogenesis and drug resistance within the BM niche. Importantly, ongoing prospective trials are evaluating its utility to inform personalized targeted and immune therapy in MM. (Keyword) Biomarkers, Tumor / Cell Differentiation / Cell Proliferation / Coculture Techniques / Humans / Mesenchymal Stem Cells / Models, Biological / Monocytes / Multiple Myeloma / Stem Cell Niche / Tumor Microenvironment (Tokushima University Institutional Repository) ● Metadata: 113971 (Link to Publication Site) ● Publication site (DOI): 10.18632/oncotarget.12643 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27764795 ● Summary page in Scopus @ Elsevier: 2-s2.0-84998693284 (Tokushima University Institutional Repository: 113971, DOI: 10.18632/oncotarget.12643, PubMed: 27764795, Elsevier: Scopus)
43.	Ryota Amachi, Masahiro Hiasa, Jumpei Teramachi, Takeshi Harada, Asuka Oda, Shingen Nakamura, Derek Hanson, Keiichiro Watanabe, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Masami Iwasa, Itsuro Endo, Takeshi Kondo, Sumiko Yoshida, Ken-ichi Aihara, Kiyoe Kurahashi, Yoshiaki Kuroda, Hideaki Horikawa, Eiji Tanaka, Masahiro Abe and Toshio Matsumoto : A vicious cycle between acid sensing and survival signaling in myeloma cells: acid-induced epigenetic alteration., Oncotarget, Vol.7, No.43, 70447-70461, 2016. (Summary) Myeloma (MM) cells and osteoclasts are mutually interacted to enhance MM growth while creating acidic bone lesions. Here, we explored acid sensing of MM cells and its role in MM cell response to acidic conditions. Acidic conditions activated the PI3K-Akt signaling in MM cells while upregulating the pH sensor transient receptor potential cation channel subfamily V member 1 (TRPV1) in a manner inhibitable by PI3K inhibition. The acid-activated PI3K-Akt signaling facilitated the nuclear localization of the transcription factor Sp1 to trigger the expression of its target genes, including TRPV1 and HDAC1. Consistently, histone deacetylation was enhanced in MM cells in acidic conditions, while repressing a wide variety of genes, including DR4. Indeed, acidic conditions deacetylated histone H3K9 in a DR4 gene promoter and curtailed DR4 expression in MM cells. However, inhibition of HDAC as well as either Sp1 or PI3K was able to restore DR4 expression in MM cells suppressed in acidic conditions. These results collectively demonstrate that acid activates the TRPV1-PI3K-Akt-Sp1 signaling in MM cells while inducing HDAC-mediated gene repression, and suggest that a positive feedback loop between acid sensing and the PI3K-Akt signaling is formed in MM cells, leading to MM cell response to acidic bone lesions. (Tokushima University Institutional Repository) ● Metadata: 113048 (Link to Publication Site) ● Publication site (DOI): 10.18632/oncotarget.11927 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27626482 ● Search Scopus @ Elsevier (PMID): 27626482 ● Search Scopus @ Elsevier (DOI): 10.18632/oncotarget.11927 (Tokushima University Institutional Repository: 113048, DOI: 10.18632/oncotarget.11927, PubMed: 27626482)
44.	Takeshi Harada, Hirokazu Miki, Q Cui, A Oda, Ryota Amachi, Jumpei Teramachi, A Bat-Erdene, K Sogabe, M Iwasa, Shiroh Fujii, Shingen Nakamura, Kumiko Kagawa, Sumiko Yoshida, I Endo, Ken-ichi Aihara, Shuji Ozaki, Toshio Matsumoto and Masahiro Abe : Expansion of Th1-like V9V2T cells by new-generation IMiDs, lenalidomide and pomalidomide, in combination with zoledronic acid., Leukemia, Vol.31, No.1, 258-262, 2016. (Link to Publication Site) ● Publication site (DOI): 10.1038/leu.2016.273 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27698446 ● Search Scopus @ Elsevier (PMID): 27698446 ● Search Scopus @ Elsevier (DOI): 10.1038/leu.2016.273 (DOI: 10.1038/leu.2016.273, PubMed: 27698446)
45.	Takeshi Harada, Shuji Ozaki, Asuka Oda, Daisuke Tsuji, Akishige Ikegame, Masami Iwasa, Kengo Udaka, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Yoshiaki Kuroda, Shigeto Kawai, Kouji Itou, Hisafumi Yamada-Okabe, Toshio Matsumoto and Masahiro Abe : Combination with a Defucosylated Anti-HM1.24 Monoclonal Antibody plus Lenalidomide Induces Marked ADCC against Myeloma Cells and Their Progenitors, PLoS ONE, Vol.8, No.12, e83905, 2013. (Summary) The immunomodulatory drug lenalidomide (Len) has drawn attention to potentiate antibody-dependent cellular cytotoxicity (ADCC)-mediated immunotherapies. We developed the defucosylated version (YB-AHM) of humanized monoclonal antibody against HM1.24 (CD317) overexpressed in multiple myeloma (MM) cells. In this study, we evaluated ADCC by YB-AHM and Len in combination against MM cells and their progenitors. YB-AHM was able to selectively kill via ADCC MM cells in bone marrow samples from patients with MM with low effector/target ratios, which was further enhanced by treatment with Len. Interestingly, Len also up-regulated HM1.24 expression on MM cells in an effector-dependent manner. HM1.24 was found to be highly expressed in a drug-resistant clonogenic "side population" in MM cells; and this combinatory treatment successfully reduced SP fractions in RPMI 8226 and KMS-11 cells in the presence of effector cells, and suppressed a clonogenic potential of MM cells in colony-forming assays. Collectively, the present study suggests that YB-AHM and Len in combination may become an effective therapeutic strategy in MM, warranting further study to target drug-resistant MM clonogenic cells. (Keyword) Aged / Aged, 80 and over / Antibodies, Monoclonal, Humanized / Antibody-Dependent Cell Cytotoxicity / Antigens, CD / Antineoplastic Combined Chemotherapy Protocols / Cell Line, Tumor / Drug Synergism / Female / GPI-Linked Proteins / Glycosylation / Humans / immunotherapy / Lenalidomide / Male / Middle Aged / Multiple Myeloma / Neoplastic Stem Cells / Side-Population Cells / Thalidomide / Up-Regulation (Tokushima University Institutional Repository) ● Metadata: 106068 (Link to Publication Site) ● Publication site (DOI): 10.1371/journal.pone.0083905 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24386306 ● Summary page in Scopus @ Elsevier: 2-s2.0-84891280322 (Tokushima University Institutional Repository: 106068, DOI: 10.1371/journal.pone.0083905, PubMed: 24386306, Elsevier: Scopus)
46.	Takeshi Harada, Shuji Ozaki, Asuka Oda, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Kyoko Takeuchi, Toshio Matsumoto and Masahiro Abe : Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma., International Journal of Hematology, Vol.97, No.6, 743-748, 2013. (Summary) Transient inflammatory reactions have been reported in a subpopulation of patients with multiple myeloma (MM) during lenalidomide (Len) plus dexamethasone (DEX) therapy. Here, we examined serum levels of Th1 (IL-2 and IFN-) and Th2 cytokines (IL-6 and TNF-) in nine refractory or relapsed MM patients treated with Len plus low-dose DEX. Six patients showed elevation of C-reactive protein (CRP) after the initiation of therapy. In these patients, IFN- and IL-6 were also elevated in two and three patients, respectively. The remaining three patients showed no appreciable changes in CRP or these cytokines. Furthermore, Len enhanced the production of both Th1 and Th2 cytokines in normal peripheral blood mononuclear cells and in patient bone marrow mononuclear cells containing primary myeloma cells and lymphocytes. These results suggest that the modulation of the Th1 and Th2 cytokine production by Len may contribute to transient inflammatory reaction in MM patients. (Link to Publication Site) ● Publication site (DOI): 10.1007/s12185-013-1321-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23609417 ● Summary page in Scopus @ Elsevier: 2-s2.0-84879151676 (DOI: 10.1007/s12185-013-1321-0, PubMed: 23609417, Elsevier: Scopus)

Academic Letter:

1.	Yusaku Maeda, Shoichiro Takao, Shiori Morita, Shin Kondo, Michiko Yamashita, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Mamiko Takahashi, Shiroh Fujii, Takeshi Harada, Hirokazu Miki, Masahiro Abe and Shingen Nakamura : Quality of skeletal muscles during allogeneic stem-cell transplantation: a pilot study, BMJ Supportive & Palliative Care, 2024. (Link to Publication Site) ● Publication site (DOI): 10.1136/spcare-2024-005070 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1136/spcare-2024-005070 (DOI: 10.1136/spcare-2024-005070)

Review, Commentary:

1.	Takeshi Harada : 骨髄腫細胞におけるCD38 の発現制御と抗CD38モノクローナル抗体に対する耐性機序, Hematology, Vol.87, No.2, 181-187, Aug. 2023. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520297437822272512 (CiNii: 1520297437822272512)
2.	Takeshi Harada and Masahiro Abe : ダラツムマブ・ボルヒアルロニダーゼアルファ配合(ダラキューロ), がん最新の薬物療法 2023-2024, 79-81, Mar. 2023.
3.	Takeshi Harada, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Myeloma-Bone Interaction: A Vicious Cycle via TAK1-PIM2 Signaling, Cancers, Vol.13, No.17, 4441, Sep. 2021. (Summary) Multiple myeloma (MM) has a propensity to develop preferentially in bone and form bone-destructive lesions. MM cells enhance osteoclastogenesis and bone resorption through activation of the RANKL-NF-κB signaling pathway while suppressing bone formation by inhibiting osteoblastogenesis from bone marrow stromal cells (BMSCs) by factors elaborated in the bone marrow and bone in MM, including the soluble Wnt inhibitors DKK-1 and sclerostin, activin A, and TGF-β, resulting in systemic bone destruction with loss of bone. Osteocytes have been drawn attention as multifunctional regulators in bone metabolism. MM cells induce apoptosis in osteocytes to trigger the production of factors, including RANKL, sclerostin, and DKK-1, to further exacerbate bone destruction. Bone lesions developed in MM, in turn, provide microenvironments suited for MM cell growth/survival, including niches to foster MM cells and their precursors. Thus, MM cells alter the microenvironments through bone destruction in the bone where they reside, which in turn potentiates tumor growth and survival, thereby generating a vicious loop between tumor progression and bone destruction. The serine/threonine kinases PIM2 and TAK1, an upstream mediator of PIM2, are overexpressed in bone marrow stromal cells and osteoclasts as well in MM cells in bone lesions. Upregulation of the TAK1-PIM2 pathway plays a critical role in tumor expansion and bone destruction, posing the TAK1-PIM2 pathway as a pivotal therapeutic target in MM. (Tokushima University Institutional Repository) ● Metadata: 117425 (Link to Publication Site) ● Publication site (DOI): 10.3390/cancers13174441 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34503251 ● Search Scopus @ Elsevier (PMID): 34503251 ● Search Scopus @ Elsevier (DOI): 10.3390/cancers13174441 (Tokushima University Institutional Repository: 117425, DOI: 10.3390/cancers13174441, PubMed: 34503251)
4.	Takeshi Harada, Teru Hideshima and Kenneth C. Anderson : Histone deacetylase inhibitors in multiple myeloma: from bench to bedside, International Journal of Hematology, Vol.104, No.3, 300-309, Sep. 2016. (Summary) Histone deacetylases (HDACs) deacetylate the lysine residues of both histones and non-histone proteins. Histone acetylation results in a loose local chromatin structure that regulates gene-specific transcription. Non-histone proteins can also be acetylated, leading to dynamic changes in their activity and stability. For these reasons, HDAC inhibition has emerged as a potential approach for the treatment of MM. Specifically, combination treatment with HDAC inhibitors and proteasome inhibitors or immunomodulatory drugs shows remarkable anti-MM activity in both preclinical and clinical settings. However, the clinical studies using non-selective HDAC inhibitors also cause unfavorable side effects in patients, leading us to develop more isoform- and/or class-selective HDAC inhibitors to enhance tolerability without diminishing anti-MM activity, thereby improving patient outcome in MM. (Keyword) Drug Therapy, Combination / Epigenomics / Histone Deacetylase Inhibitors / Humans / Immunologic Factors / Multiple Myeloma / Proteasome Inhibitors / Translational Medical Research (Link to Publication Site) ● Publication site (DOI): 10.1007/s12185-016-2008-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27099225 ● Search Scopus @ Elsevier (PMID): 27099225 ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-016-2008-0 (DOI: 10.1007/s12185-016-2008-0, PubMed: 27099225)

Proceeding of International Conference:

1.	Shingen Nakamura, Yusaku Maeda, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Hikaru Yagi, Shiro Fujii, Takeshi Harada and Hirokazu Miki : False-positive aspergillus galactomannan test in multiple myeloma, ID week 2024, Oct. 2024.
2.	Takeshi Harada, Asuka Oda, Yosuke Matsushita, Ryohei Sumitani, Yusuke Inoue, Tomoyo Hara, Masahiro Oura, Kimiko Sogabe, Tomoko Maruhashi, Mamiko Takahashi, Kiyoe Kurahashi, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Masahiro Hiasa, Jumpei Teramachi, Toyomasa Katagiri and Masahiro Abe : ADAR1-dsRNA metabolism in myeloma cells with 1q amplification: a novel therapeutic target, 19th International Myeloma Society Annual Meeting, Aug. 2022.
3.	Kotaro Tanimoto, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Asuka Oda, Takeshi Harada, Yoshiki Higa, Kimiko Sogabe, Masahiro Oura, Ryohei Sumitani, Tomoyo Hara, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : Mechanical unloading promotes bone destruction and myeloma tumor expansion, Cancer and bone society young investigator symposium, Online, Feb. 2022.
4.	Hirofumi Tenshin, Takeshi Harada, Yusuke Inoue, Jumpei Teramachi, Masahiro Hiasa, Sou Shimizu, Emiko Nakaue, Kotaro Tanimoto, Yoshiki Higa, Masahiro Oura, Kimiko Sogabe, Tomoyo Hara, Ryohei Sumitani, Tomoko Maruhashi, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Targeting SLAMF7 to disrupt myeloma-osteoclast interaction: elotuzumabs ADCC activity with Th1-like gamma delta T cells towards osteoclasts and myeloma cells., Cancer and bone society young investigator symposium, Feb. 2022.
5.	Takeshi Harada, Yusuke Inoue, Hirofumi Tenshin, Asuka Oda, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Novel strategy of elotuzumab and zoledronic acid with Th1-like T cells against myeloma, 18th International Myeloma Workshop, Wien, Sep. 2021.
6.	Takeshi Harada, Yusuke Inoue, Hirofumi Tenshin, Asuka Oda, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Induction of elotuzumabs ADCC activity by Th1-like T cells towards osteoclasts as well as myeloma cells, EHA2021 Virtual Congress, Jun. 2021.
7.	Takeshi Harada and Masahiro Abe : Targeting osteoclasts and myeloma cells by CELMoDs plus zoledronic acid-inducible Th1-like γδT cells in combination with elotuzumab, The 12th JSH International Symposium 2021, May 2021.
8.	Hirofumi Tenshin, Takeshi Harada, 井上雄介, Jumpei Teramachi, Masahiro Hiasa, 小田明日香, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Masahiro Oura, Kimiko Sogabe, Tomoyo Hara, Tomoko Maruhashi, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : The anti-SLAMF7 elotuzumab enhances ADCC activity with Th1-like γδT cells towards osteoclasts and myeloma cells., The European Calcified Tissue Society 2021 Digital Congress 2021, web, Mar. 2021.
9.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Takeshi Harada, Eiji Tanaka, Kotaro Tanimoto, Sou Shimizu, Masahiro Oura, Kimiko Sogabe, Masahiro Abe, Toshio Matsumoto and Itsuro Endo : The novel therapeutic approaches with TAK1 inhibition against the aberrant NLRP3 inflammasome activation in rheumatoid arthritis, ECTS 2020 Digital Congress, Oct. 2020.
10.	Takeshi Harada, Asuka Oda, Hiroto Ohguchi, Yohann Grondin, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Hirokazu Miki, Kumiko Kagawa, Shuji Ozaki, Teru Hideshima, Kenneth C. Anderson and Masahiro Abe : Novel therapeutic rationale for targeting HDAC1 and PIM2 in multiple myeloma, 61th ASH Annual Meeting & Exposition, Orlando, Dec. 2019. (Link to Publication Site) ● Publication site (DOI): 10.1182/blood-2019-127679 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1182/blood-2019-127679 (DOI: 10.1182/blood-2019-127679)
11.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Asuka Oda, Ashtar Mohannad, Kotaro Tanimoto, Soh Shimizu, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : The role of NLRP3 inflammasome activation in joint inflammation and destruction in rheumatoid arthritis: novel therapeutic approaches with TAK1 inhibition., 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting, Oct. 2019.
12.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Asuka Oda, Ashtar Mohannad, Kotaro Tanimoto, Masami Iwasa, Bat-Erdene Ariunzaya, Takeshi Harada, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1 inhibition effectively alleviates joint inflammation as well as bone destruction in rheumatoid arthritis: Suppression of NLRP3 inflammasome-mediated inflammation and osteoclastic bone resorption, American Society for Bone and Mineral Society Annual meeting 2019, Orlando, Florida, USA,, Sep. 2019.
13.	Jumpei Teramachi, Soh Shimizu, Hirofumi Tenshin, Bat-Erdene Ariunzaya, Masahiro Hiasa, Kotaro Tanimoto, Oda Asuka, Takeshi Harada, Mohannad Ashtar, Kotaro Tanimoto, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : A progressive auto-amplification loop in TAK1 expression and activation in MM cells., ASBMR 2019,, Orlando, Florida, USA., Sep. 2019.
14.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Oda Asuka, Ashtar Mohannad, Kotaro Tanimoto, Masami Iwasa, Bat-Erdene Ariunzaya, Takeshi Harada, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1 inhibition effectively alleviates joint inflammation as well as bone destruction in rheumatoid arthritis: Suppression of NLRP3 inflammasome-mediated inflammation and osteoclastic bone resorption., ASBMR 2019,, Orlando, Florida, USA., Sep. 2019.
15.	Takeshi Harada, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Shuji Ozaki, Teru Hideshima, C. Kenneth Anderson and Masahiro Abe : Targeting myeloma metabolisms regulated by HDAC1-IRF4 axis can be a novel therapeutic strategy, 17th International Myeloma Workshop, Sep. 2019.
16.	Mohannad Ashtar, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Oda Asuka, Iwasa Masami, Takeshi Harada, Bat-Erdene Ariunzaya, Kimiko Sogabe, Masahiro Oura, Shiroh Fujii, Kumiko Kagawa, Shingen Nakamura, Hirokazu Miki, Toshio Matsumoto, Masahiro Abe and Eiji Tanaka : Peri-implantitis and the role of Febuxostat in osteoclast differentiation., AEEDC Dubai World Orthodontic Conference, Dubai, UAE, Feb. 2019.
17.	Takeshi Harada, Asuka Oda, Yohann Grondin, Jumpei Teramachi, Ariunzaya Bat-Erdene, Masami Iwasa, Masahiro Oura, Shingen Nakamura, Kumiko Kagawa, Yasunobu Okamoto, Kimiko Sogabe, Shiroh Fujii, Hirokazu Miki, Shuji Ozaki, Teru Hideshima, Kenneth C. Anderson and Masahiro Abe : The critical role of the HDAC1-IRF4-Pim-2 axis in myeloma cell growth and survival: therapeutic impacts of targeting the HDAC1-IRF4-Pim-2 axis, 60th ASH Annual Meeting & Exposition, San Diego, Dec. 2018.
18.	Shingen Nakamura, Hirokazu Miki, Ariunzaya Bat-Erdene, Yasunobu Okamoto, Kimiko Sogabe, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiroh Fujii, Kumiko Kagawa and Masahiro Abe : Alteration of muscle mass after chemotherapy in patients with newly diagnosed multiple myeloma., Esmo asia 2018, Nov. 2018.
19.	Jumpei Teramachi, Hirofumi Tenshin, Masahiro Hiasa, Oda Asuka, Bat-Erdene Ariunzaya, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Toshio Matsumoto and Masahiro Abe : Disruption of a progressive vicious cycle between myeloma tumor growth and bone destruction by TAK1 inhibition, ASBMR 2018 Annual Meeting, Montreal, Sep. 2018.
20.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Oda Asuka, Ashtar Mohannad, Kotaro Tanimoto, Iwasa Masami, Bat-Erdene Ariunzaya, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Opposite effects of TRAIL on the Sp-1-c-FLIP survival pathway in myeloma cells and osteoclasts., ASBMR 2018 Annual Meeting, Montreal, Sep. 2018.
21.	Takeshi Harada, Oda Asuka, Jumpei Teramachi, Bat-Erdene Ariunzaya, Iwasa Masami, Oura Masahiro, Shingen Nakamura, Kumiko Kagawa, Okamoto Yasunobu, Kimiko Sogabe, Shiroh Fujii, Hirokazu Miki, Hideshima Teru, Anderson C. Kenneth and Masahiro Abe : Selective inhibition of class-I HDAC induces myeloma cell death through targeting IRF4-Pim-2 axis, The 9th JSH International Symposium 2018 in Kyoto, Jul. 2018. (Keyword) Multiple myeloma / Class-I HDAC / IRF4 / Pim2
22.	Jumpei Teramachi, Hirofumi Tenshin, Masahiro Hiasa, Oda Asuka, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Tatsuji Haneji, Itsuro Endo, Toshio Matsumoto and Masahiro Abe : Therapeutic impact of TAK1 inhibition on myeloma tumor progression and bone destruction, 8th International Workshop on Advances in the Molecular Pharmacology and Therapeutics of Bone and other Musculoskeletal Diseases and Cancer and Bone Society 2018 Meeting, Oxford, Jun. 2018.
23.	Jumpei Teramachi, Masahiro Hiasa, Oda Asuka, Hirofumi Tenshin, Ryota Amachi, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Tatsuji Haneji, Toshio Matsumoto and Masahiro Abe : TAK1 inhibition impairs myeloma cell-bone marrow interaction to reduce myeloma tumor growth and bone destruction, American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting, Denver, Sep. 2017.
24.	Jumpei Teramachi, Masahiro Hiasa, Oda Asuka, Hirofumi Tenshin, Ryota Amachi, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Tatsuji Haneji, Toshio Matsumoto and Masahiro Abe : Therapeutic impact of TAK1 inhibition on myeloma tumor progression and bone destruction, International Society for Experimental Hematology 46th Annual Scientific Meeting, Frankfurt, Aug. 2017.
25.	Jumpei Teramachi, Masahiro Hiasa, Oda Asuka, Hirofumi Tenshin, Ryota Amachi, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Akihito Yamamoto, Tatsuji Haneji, Toshio Matsumoto and Masahiro Abe : Therapeutic impact of TAK1 inhibition on myeloma tumor progression and bone destruction, Cancer and Bone Society Conference 2017, Indianapolis, May 2017.

Proceeding of Domestic Conference:

1.	住谷龍平, Shingen Nakamura, Masahiro Oura, Kimiko Sogabe, 高橋真美子, Shiroh Fujii, Takeshi Harada, Hirokazu Miki and 安倍正博 : 周期的な発熱，血小板減少，高LDH血症で発症したびまん性大細胞型B細胞リンパ腫の1例, 第128回日本内科学会四国地方会,
2.	Yusaku Maeda, Shingen Nakamura, Saki Saijo, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 高橋真美子, Shiroh Fujii, Takeshi Harada and Hirokazu Miki : 多職種による集学的ケアを行ったインヒビター保有重症先天性血友病Aの1例, 第129回内科学会四国地方会,
3.	阪本朋香, Yoshie Imai, 三木こずえ, Shiroh Fujii, Hirokazu Miki, Kimiko Sogabe, Masahiro Oura, Ryohei Sumitani, 八木ひかる, 高橋真美子, Takeshi Harada, 前田悠作, Shingen Nakamura and Ken-ichi Matsuoka : 治療過程にある多発性骨髄腫患者が治療を続ける意味, 第39回日本がん看護学会学術集会, Feb. 2025.
4.	明石和子, Yoshie Imai, Shingen Nakamura, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, Takeshi Harada, Shiroh Fujii and Hirokazu Miki : 初回再発した老年期の造血器腫瘍患者が捉える化学療法への構え, 第9回日本がんサポーティブケア学会学術集会, May 2024.
5.	Ryohei Sumitani, Hirokazu Miki, Kazumi Okamura, 前田悠作, Masahiro Oura, Kimiko Sogabe, 八木ひかる, 高橋真美子, 丸橋朋子, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Takeshi Oya, Masahiro Abe and 佐藤亜紀 : KRAS変異を認めた治療抵抗性Rosai-Dorfman病の1例, 臨床血液, Vol.65, No.5, 473, May 2024.
6.	明石和子, Yoshie Imai, Shingen Nakamura, 西條早希, 前田悠作, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, Takeshi Harada, Shiroh Fujii and Hirokazu Miki : 初回再発した成人期の造血器腫瘍患者が捉える化学療法への構え, 第21回日本臨床腫瘍学会学術集, Feb. 2024.
7.	Shingen Nakamura, 手束宏明, 山上圭, Yuishin Izumi, 西條早希, 前田悠作, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 高橋真美子, 藤井志朗, Takeshi Harada and 三木浩和 : 免疫再構築症候群により急速な経過で死亡に至ったHIV関連進行性多巣性白質脳症の一剖検例, 日本エイズ学会誌, Vol.25, No.4, 461, Nov. 2023. (Keyword) AIDS(合併症,薬物療法,病理学) 白質脳症-進行性多巣性(病因,薬物療法,病理学) 剖検免疫再構築症候群(病因,病理学) ヒト中年(45∼64) 男
8.	明石和子, Yoshie Imai, Shingen Nakamura, 西條早希, 前田悠作, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, Takeshi Harada, Shiroh Fujii and Hirokazu Miki : 再発・難治性造血器腫瘍患者が捉えるアドバンス・ケア・プランニング, 第61回日本癌治療学会学術集会, Oct. 2023.
9.	Kim SooHa, Jumpei Teramachi, Masahiro Hiasa, Hirofumi Tenshin, Emiko Nakaue, TANAKA Mariko, NAKAGAWA Motosumi, Itsuro Endo, Takeshi Harada, Eiji Tanaka and Masahiro Abe : Molecular mechanisms for generation of non-permissive niche for myeloma cells by activated osteoblasts., The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 173, Jul. 2023.
10.	Ryohei Sumitani, Shingen Nakamura, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, Shiroh Fujii, Takeshi Harada, Hirokazu Miki and Masahiro Abe : 周期的な発熱，血小板減少，高LDH血症で発症したびまん性大細胞型B細胞リンパ腫の1例, 第128回日本内科学会四国地方会, Jul. 2023.
11.	Ryohei Sumitani, Shingen Nakamura, 林成樹, Masahiro Oura, Kimiko Sogabe, 高橋真美子, Takeshi Harada, 藤井志朗, 三木浩和, 東航平 and 安倍正博 : Lipiodolでのリンパ管造影により難治性乳糜腹水が軽快した濾胞性リンパ腫, 臨床血液, Vol.64, No.6, 560, Jun. 2023. (Keyword) エチヨード化油(診断的利用,治療的利用) 乳び腹水(治療,X線診断,合併症) リンパ管造影リンパ腫-濾胞性(合併症) ヒト高齢者(65∼79) 女
12.	林成樹, Ryohei Sumitani, Masahiro Oura, Takeshi Harada, Shingen Nakamura, Ayaka Mori, Masanori Tamaki and Masahiro Abe : ITP，自己免疫性出血病F13に続発しTAFRO症候群を発症した1例, 第127回日本内科学会四国地方会, Dec. 2022.
13.	佃恵里加, 李悦子, 瀧本朋美, 小田直輝, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki and Masahiro Abe : ダラツムマブ投与患者における間接抗グロブリン試験干渉期間の検討, Japanese Journal of Transfusion and Cell Therapy, Vol.68, No.6, 582-583, Dec. 2022.
14.	Mamiko Takahashi, Shingen Nakamura, Shin Kondo, Masafuumi Nakamura, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Takeshi Harada, Shiroh Fujii, Hirokazu Miki and Masahiro Abe : Importance of skeletal muscle mass during chemotherapies in patients with hematological malignancies, JSH2022, Oct. 2022.
15.	Takeshi Harada, Ryohei Sumitani, Asuka Oda, Yusuke Inoue, Masahiro Oura, Kimiko Sogabe, Tomoko Maruhashi, Mamiko Takahashi, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Shuji Ozaki, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : The therapeutic potential targeting ADAR1-dsRNA metabolism in myeloma cells with 1q amplification, The 84th Annual Meeting of the Japanese Society of Hematology, Oct. 2022.
16.	新居寛子, 髙橋真美子, Shiroh Fujii, Kimiko Sogabe, 林成樹, Ryohei Sumitani, Masahiro Oura, Takeshi Harada, Shingen Nakamura, 安積麻衣, 湊将典, Hirokazu Miki and Masahiro Abe : ループス腎炎に対してミコフェノール酸モフェチル投与中に発症した他の医原性免疫不全関連リンパ増殖性疾患の1例, 第265回徳島医学会学術集会, Jul. 2022.
17.	Emiko Nakaue, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi, Takeshi Harada, Yusuke Inoue, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : プロテアソーム阻害薬による骨髄腫骨病変部選択的骨形成誘導活性の検討, 第40回日本骨代謝学会学術集会, 141, Jul. 2022.
18.	Yoshiki Higa, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Takeshi Harada, 小田明日香, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : キサンチンオキシダーゼ(XO)阻害薬febuxostatによる脂肪細胞分化と骨芽細胞分化の制御機構, 第40回日本骨代謝学会学術集会, Jul. 2022.
19.	TANAKA Mariko, Masahiro Hiasa, Kotaro Tanimoto, Hirofumi Tenshin, Sou Shimizu, Yoshiki Higa, Emiko Nakaue, KIMU Suha, Jumpei Teramachi, Takeshi Harada, Shingen Nakamura, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 不動は骨髄腫骨病変部DPP-4発現増加と骨髄腫の腫瘍進展・髄外播種を加速させる, 第40回日本骨代謝学会学術集会, Jul. 2022.
20.	Takeshi Harada, Hirofumi Tenshin, Yusuke Inoue, Ryohei Sumitani, Emiko Nakaue, Jumpei Teramachi, Masahiro Hiasa, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Production of SLAMF7 by osteoclasts and development of novel treatment targeting SLAMF7 against myeloma bone disease, 第40回日本骨代謝学会学術集会, Jul. 2022.
21.	Ryohei Sumitani, Makiko Mizuguchi, Masahiro Oura, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Toshihiro Hashimoto, Takeshi Harada and Masahiro Abe : 126, 第126回日本内科学会四国地方会, Jun. 2022.
22.	中村昌史, Hirokazu Miki, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 高橋真美子, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, 西尾進, Tetsu Tomonari and Masahiro Abe : ALアミロイドーシスの肝病変の評価における超音波エラストグラフィの有用性, The Japanese Journal of Clinical Hematology, Vol.63, No.6, 685-686, Jun. 2022. (Keyword) 肝臓疾患(超音波診断,薬物療法) 組織弾性イメージング *アミロイドーシス-免疫グロブリン軽鎖(超音波診断,薬物療法) ヒト中年(45∼64) 男女
23.	Shingen Nakamura, HORI Taiki, Masafumi Nakamura, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Tomoko Maruhashi, 高橋真美子, Shiroh Fujii, Hirokazu Miki, Takeshi Harada and Masahiro Abe : Humoral response of the mRNA vaccine against SARS-CoV-2 in patients with plasma cell dyscrasia, The 47th annual meeting of Japanese Society of Myeloma, May 2022.
24.	Hirofumi Tenshin, Takeshi Harada, 井上雄介, 菊池次郎, 小田明日香, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 高橋真美子, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Masahiro Hiasa, Jumpei Teramachi, 鈴木敦, 角川学士, 峯畑健一, 古川雄祐 and Masahiro Abe : Osteoclasts robustly express SLAMF7 and secrete soluble SLAMF7, The 47th Annual Meeting of the Japanese Society of Myeloma, May 2022.
25.	井上雄介, Takeshi Harada, Hirofumi Tenshin, 小田明日香, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 高橋真美子, Shiroh Fujii, Hirokazu Miki, Shingen Nakamura, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Leverage of Th1-like γδT cells into antibody-mediated immunotherapy against myeloma, The 47th Annual Meeting of the Japanese Society of Myeloma, May 2022.
26.	Takeshi Harada, Ryohei Sumitani, Asuka Oda, Inoue Yusuke, Masahiro Oura, Kimiko Sogabe, Tomoko Maruhashi, Takahashi Mamiko, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Therapeutic impact of targeting RNA editing enzyme ADAR1 on myeloma cells with 1q amplification, 第47回日本骨髄腫学会学術集会, May 2022.
27.	Jumpei Teramachi, Hirofumi Tenshin, Masahiro Hiasa, 小田明日香, Sou Shimizu, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Takeshi Harada and Masahiro Abe : TAK1 阻害は骨髄腫の細胞間相互作用による骨破壊と薬剤耐性を改善する, 第47回日本骨髄腫学会学術集会, May 2022.
28.	丸橋朋子, Hirokazu Miki, Kimiko Sogabe, Takeshi Harada, 小田明日香, Shingen Nakamura, 中村昌史, Ryohei Sumitani, Masahiro Oura, 高橋真美子, Shiroh Fujii and Masahiro Abe : 骨髄腫細胞のプロテアソーム阻害薬への抵抗性の機序と温熱療法によるその克服の可能性, 第47回日本骨髄腫学会学術集会, May 2022.
29.	Shingen Nakamura, 堀太貴, 中村昌史, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 髙橋真美子, Shiroh Fujii, Hirokazu Miki, Takeshi Harada and Masahiro Abe : 形質細胞疾患における新型コロナワクチンの有効性, 第47回日本骨髄腫学会学術集会, May 2022.
30.	Hirokazu Miki, Shingen Nakamura, 中村昌史, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, 丸橋朋子, Takeshi Harada, Shiroh Fujii, 西尾進, 友成哲 and Masahiro Abe : 肝臓アミロイドーシスに対する超音波エラストグラフィを用いた非侵襲的診断法の有用性, 第47回日本骨髄腫学会学術集会, May 2022.
31.	Yoshiki Higa, Masahiro Hiasa, Hirofumi Tenshin, Kotaro Tanimoto, Sou Shimizu, Jumpei Teramachi, Takeshi Harada, 小田明日香, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : Critical role of the xanthine oxidase-ROS axis in perturbation of bone marrow milieu in myeloma, International Journal of Myeloma, Vol.12, No.3, 149, May 2022.
32.	Shingen Nakamura, 堀太貴, 中村昌史, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 高橋真美子, Shiroh Fujii, Hirokazu Miki, Takeshi Harada, Ken-ichi Aihara and Masahiro Abe : 形質細胞異常症患者におけるSARS-CoV-2に対するmRNAワクチンの液性免疫応答の評価(Humoral response of the mRNA vaccine against SARS-CoV-2 in patients with plasma cell dyscrasia), International Journal of Myeloma, Vol.12, No.3, 199, May 2022. (Keyword) 予防接種単クローン性免疫グロブリン血症-良性(免疫学) 液性免疫アミロイドーシス-免疫グロブリン軽鎖(免疫学) *COVID-19ワクチン(治療的利用,薬理学)
33.	Emiko Nakaue, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Takeshi Harada, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Ryohei Sumitani, 丸橋朋子, Masahiro Oura, Kimiko Sogabe, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka and Masahiro Abe : The impact of pulsatile proteasome inhibitor on bone metabolism, International Journal of Myeloma, Vol.12, No.3, 152, May 2022. (Keyword) 骨髄腫-多発性(薬物療法,病理学) / 骨組織リモデリング / パルス療法(薬物療法) / Proteasome Inhibitors(治療的利用,薬理学) / Homo sapiens
34.	Hirofumi Tenshin, Takeshi Harada, 井上雄介, 菊池次郎, 小田明日香, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 高橋真美子, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Masahiro Hiasa, Jumpei Teramachi, 鈴木敦, 角川学士, 峯畑健一, 古川雄祐 and Masahiro Abe : 破骨細胞はSLAMF7を強発現し可溶性SLAMF7を産生する(Osteoclasts robustly express SLAMF7 and secrete soluble SLAMF7), International Journal of Myeloma, Vol.12, No.3, 150, May 2022. (Keyword) 骨髄腫-多発性(遺伝学,病理学) 破骨細胞 Signaling Lymphocytic Activation Molecule Family(血液) SLAMF7 Protein(血液) ヒト
35.	高原由実子, Hirokazu Miki, Shingen Nakamura, 中村昌史, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 高橋真美子, 丸橋朋子, Takeshi Harada, Shiroh Fujii, Masahiro Abe, 岡本秀樹, 岡田直人, 矢野由美子, 高橋真理, 青田桂子 and Shuji Ozaki : HIV感染症および後天性免疫不全症候群患者の臨床的特徴と今後の課題, Shikoku Acta Medica, Vol.78, No.1-2, 89, Apr. 2022.
36.	Ryohei Sumitani, Takeshi Harada, 中村昌史, 水口槙子, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 髙橋真美子, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Mio Yada, Yoshihiro Matsudate, Hisanori Uehara and Masahiro Abe : 少量methotrexate療法が有効であった進行期原発性皮膚未分化大細胞型リンパ腫., The Japanese Journal of Clinical Hematology, Vol.63, No.6, 536-543, Mar. 2022. (Summary) 進行期の原発性皮膚未分化大細胞リンパ腫(pcALCL)に対する標準治療は定まっていない．症例は71歳,男性．多発性の皮膚紅斑と結節病変を認め,左耳介後部からの生検でリンパ腫性丘疹症(LyP)と診断された．局所電子線照射にて全ての病変は消退したが,5ヵ月後に両内眼角に結節病変が出現し,同部位の生検ではCD30陽性大型細胞が大部分を占めpcALCLと診断された．PET/CTにて右口蓋扁桃腫大,頸部,鼠径部の表在リンパ節腫大およびFDG集積を認め,TNM分類T3bN3M0であった．慢性閉塞性肺疾患による呼吸機能低下と肺炎を反復していたため,多剤併用化学療法ではなくmethotrexate(MTX)15mg/週の内服療法を選択した．皮膚,リンパ節病変は縮小し,副作用なく長期間病勢コントロールが可能であった．pcALCLの標準治療は確立されていないが様々な治療法が開発されてきており,少量MTX療法は呼吸器感染症を繰り返すフレイルな患者に有用であった．LyPにpcALCLが続発する機序や本疾患群に対する少量MTX療法の作用機序の解明が望まれる．(著者抄録) (Keyword) Etoposid / Methotrexate / 顔面腫瘍 / lung disease / 皮膚疾患-顔面 / 皮膚腫瘍 / 扁桃腫瘍 / 放射線療法 / Folic Acid / リンパ腫-未分化大細胞 / 心筋症-たこつぼ型 / PET-CT検査 / フレイル / Homo sapiens / 高齢者 (Link to Publication Site) ● Publication site (DOI): 10.11406/rinketsu.63.536 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.11406/rinketsu.63.536 (DOI: 10.11406/rinketsu.63.536)
37.	高原由実子, Hirokazu Miki, Shingen Nakamura, 中村昌史, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, 丸橋朋子, 岡本秀樹, Naoto Okada, 矢野由美子, 高橋真理, Takeshi Harada, Shiroh Fujii, Keiko Aota, Shuji Ozaki and Masahiro Abe : HIV感染症および後天性免疫不全症候群患者の臨床的特徴と今後の課題., --- 264 ( 3 ) ---, 第264回徳島医学会学術集会(令和3年度冬期), 2022年2月20日(Web開催), Feb. 2022.
38.	Sou Shimizu, Jumpei Teramachi, Takeshi Harada, 小田明日香, Hirofumi Tenshin, Masahiro Hiasa, Kotaro Tanimoto, Yoshiki Higa, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : The critical roles of the TAK1-CIP2A axis in MM cell growth and survival and osteoclastogensis, 第83回日本血液学会学術集会, BPA-3-3, Sep. 2021.
39.	Kimiko Sogabe, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, 小田明日香, 井上雄介, Ryohei Sumitani, 丸橋朋子, Masahiro Oura, Shiroh Fujii, Kumiko Kagawa, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Resumption of myeloma cell sensitivity to proteasome inhibitors by PIM and Akt inhibition, The 83rd Annual Meeting of the Japanese Society of Hematology, Sep. 2021.
40.	Yoshiki Higa, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Takeshi Harada, 小田明日香, 大浦雅弘, Kimiko Sogabe, Itsuro Endo, Toshio Matsumoto, Masahiro Abe and Eiji Tanaka : Critical roles of the XO-ROS axis in the pathology of bone loss in myeloma, 第83回日本血液学会学術集会, BPA-3-4, Sep. 2021.
41.	Hirofumi Tenshin, 寺町順平日浅雅博小田明日香原田武志, Masahiro Hiasa, 小田明日香, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Eiji Tanaka, Itsuro Endo, Toshio Matsumoto and Masahiro Abe : NLRP3 inflammasome aggravates osteoclastic bone destruction in myeloma, 日本血液学会学術集会83回 Page 83回 Page OS2-4B-4(2021.09), Sep. 2021.
42.	Kotaro Tanimoto, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Takeshi Harada, 小田明日香, Masahiro Oura, Kimiko Sogabe, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe : Extraosseous dissemination of myeloma by mechanical unloading, 日本血液学会学術集会83回 Page 83回 Page OS2-11C-3(2021.09), Sep. 2021.
43.	Takeshi Harada, Yusuke Inoue, Hirofumi Tenshin, Asuka Oda, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Expansion of γδT cells by CELMoDs and enhancement of their anti-myeloma effects by elotuzumab, The 83rd Annual Meeting of Japanese Society of Hematology, Sep. 2021.
44.	Shingen Nakamura, 上野宜久, Sumiko Yoshida, 中村昌史, 水口槙子, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 高橋真美子, 丸橋朋子, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, 広津崇亮 and Masahiro Abe : 血液がんにおける線虫がん検査 N-NOSEの検討(Detection of hematological malignancies using N-NOSE(Nematode-NOSE)), 日本血液学会学術集会, OS1-11B-2, Sep. 2021. (Keyword) 検尿走化性 Caenorhabditis elegans 造血器腫瘍(診断) ヒト男女
45.	Hirokazu Miki, Shingen Nakamura, Shiroh Fujii, 中村昌史, 水口槙子, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, 丸橋朋子, Takeshi Harada, Kumiko Kagawa, Nishio Susumu, Tetsu Tomonari and Masahiro Abe : 肝臓アミロイドーシスに対する超音波エラストグラフィの診断的有用性., 第83回日本血液学会学術集会, OS1-8D-2, Sep. 2021.
46.	Kimiko Sogabe, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, 小田明日香, 井上雄介, Ryohei Sumitani, 丸橋朋子, Masahiro Oura, Shiroh Fujii, Kumiko Kagawa, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : PIMとAkt阻害による骨髄腫細胞のプロテアソーム阻害薬感受性の増強(Sensitization of myeloma cells to proteasome inhibitors by PIM and Akt inhibition), 日本血液学会学術集会, OS2-11D-3, Sep. 2021.
47.	Takeshi Harada, Yusuke Inoue, Hirofumi Tenshin, Asuka Oda, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Development of combinatory treatment of Th1-like γδT cells with elotuzumab against osteoclasts as well as myeloma cells, 第46回日本骨髄腫学会学術集会, May 2021.
48.	Hirokazu Miki, Shingen Nakamura, 中村昌史, 水口槙子, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 髙橋真美子, 丸橋朋子, Takeshi Harada, Shiroh Fujii, Kumiko Kagawa, Masateru Kondo, Naoto Okada, Yoshimi Bando, Itsuro Endo and Masahiro Abe : The importance of retaining physical functions to prevent SRE in multiple myeloma., 第46回日本骨髄腫学会学術集会, May 2021.
49.	Kimiko Sogabe, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, 小田明日香, 井上雄介, Ryohei Sumitani, Masahiro Oura, Shiroh Fujii, Kumiko Kagawa, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi, 李政樹, 飯田真介 and Masahiro Abe : 骨髄腫細胞のプロテアソーム阻害薬の耐性機序におけるPIM2とAkt活性およびNRF2蓄積の役割(Mechanisms for the resistance to proteasome inhibitors in myeloma cells: the role of PIM2 and Akt kinase activation and NRF2 accumulation), International Journal of Myeloma, Vol.11, No.2, 85, May 2021. (Keyword) 癌原遺伝子タンパク質骨髄腫-多発性(遺伝学,実験的) Protein-Serine-Threonine Kinases 抗腫瘍剤耐性 c-akt癌原遺伝子タンパク質 NF-E2-Related Factor 2 Proteasome Inhibitors(薬理学) *PIM2 Protein
50.	石田卓也, Hirokazu Miki, 髙橋真美子, 中村昌史, 水口槙子, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 丸橋朋子, 岡本秀樹, Naoto Okada, 矢野由美子, 高橋真理, Tetsu Tomonari, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Kumiko Kagawa, Keiko Aota, Hiroyoshi Watanabe and Masahiro Abe : HIV感染血友病患者における臨床的特徴と今後の課題, 第262回徳島医学会学術集会, Mar. 2021.
51.	Maruhashi Tomoko, Shiroh Fujii, Kumiko Kagawa, Nakamura Masafumi, Shiyori Kawata, Makiko Mizuguchi, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Takahashi Mamiko, Takeshi Harada, Shingen Nakamura, Hirokazu Miki and Masahiro Abe : 造血幹細胞移植(allo-SCT)が奏効したMLL遺伝子変異合併CML急性転化(CML-BP)の2例, 第43回日本造血細胞移植学会総会, Mar. 2021.
52.	清重尚希, Ryohei Sumitani, 水口槙子, 中村昌史, Masahiro Oura, Kimiko Sogabe, 高橋真美子, Takeshi Harada, Shiroh Fujii, 賀川久美子, Masahiro Abe, Shingen Nakamura, Hirokazu Miki, 曽賀愛未, 一宮由貴 and Yuri Yamamoto : 急性転化をきたしたAYA世代慢性骨髄性白血病の1例, Shikoku Acta Medica, Vol.76, No.5-6, 354-355, Dec. 2020. (Keyword) 同種移植抗腫瘍剤(治療的利用) *白血病-BCR-ABL陽性慢性骨髄性(診断,治療,薬物療法) 急性転化(白血病) 障害者の子供造血幹細胞移植家族介護者ヒト青年期(13~18) 女
53.	Hirokazu Miki, 悦子李, 佃恵里加, 小田直輝, 瀧本朋美, 中村昌史, 水口槙子, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, 高橋真美子, Takeshi Harada, Shiroh Fujii, Kumiko Kagawa, Masahiro Abe and Shingen Nakamura : Daratumumab投与による輸血関連検査への影響とその対策, Shikoku Acta Medica, Vol.76, No.5-6, 341, Dec. 2020. (Keyword) Coombsテスト / 骨髄腫-多発性(診断,薬物療法) / Daratumumab(治療的利用) / ヒト / 中年(45~64) / 高齢者(65~79) / 高齢者(80~) / 男 / 女
54.	市原聖也, Ryohei Sumitani, 中村昌史, 水口槙子, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa and Masahiro Abe : ウイルス関連血球貪食症候群が疑われたアグレッシブNK細胞白血病の1例, 第123回日本内科学会四国地方会, Nov. 2020.
55.	Kimiko Sogabe, Shingen Nakamura, Shiroh Fujii, Hirokazu Miki, 小田明日香, Takeshi Harada, Ryohei Sumitani, Masahiro Oura, Kumiko Kagawa, Hirofumi Tenshin, Jumpei Teramachi, Masaki Ri, Shinsuke Iida and Masahiro Abe : Immediate accumulation of anti-apoptotic PIM2 in myeloma cells by proteasome inhibitors, 第82回日本血液学会学術集会, Oct. 2020.
56.	Sou Shimizu, Jumpei Teramachi, Takeshi Harada, 小田明日香, Hirofumi Tenshin, Masahiro Hiasa, Kotaro Tanimoto, Yoshiki Higa, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 骨髄腫細胞のPP2A阻害因子CIP2A発現誘導を介するTAK1活性化増強機構, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 149, Oct. 2020.
57.	Kotaro Tanimoto, Masahiro Hiasa, Hirofumi Tenshin, Mohannad Ashtar, Sou Shimizu, Yoshiki Higa, Jumpei Teramachi, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 不動は骨吸収と骨髄腫進展を促進させる, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 149, Oct. 2020.
58.	Hirofumi Tenshin, Mohannad Ashtar, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Sou Shimizu, Yoshiki Higa, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 抗腫瘍薬が誘導するROSは破骨細胞分化を促進する:Xanthine oxidase阻害剤febuxostatの治療効果．, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 148, Oct. 2020.
59.	Takeshi Harada, Yusuke Inoue, Hirofumi Tenshin, Asuka Oda, Masahiro Oura, Kimiko Sogabe, Ryohei Sumitani, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Masahiro Hiasa, Jumpei Teramachi and Masahiro Abe : Versatile anti-myeloma effects by elotuzumab: impact on γδT cells and osteoclasts, The 82nd Annual Meeting of Japanese Soceity of Hematology, Oct. 2020.
60.	Kiyoe Kurahashi, 村井純平, 堀太貴, Ryohei Sumitani, Takeshi Harada, Shingen Nakamura, Mai Kanai, Akiko Sakurai, 原倫世, 桝田志保, Sumiko Yoshida, Itsuro Endo, 松本俊夫, Masahiro Abe and Seiji Fukumoto : 高1,25(OH)2D血症による高Ca血症を来したホジキンリンパ腫の一例, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 150, Oct. 2020. (Keyword) Calcitriol Dacarbazine(治療的利用) Doxorubicin(治療的利用) Hodgkin病(合併症,病理学,薬物療法) Vinblastine(治療的利用) *高カルシウム血症(病因,病理学,薬物療法) 免疫組織化学 Brentuximab Vedotin(治療的利用) ヒト高齢者(65~79) 男
61.	Hirofumi Tenshin, アシテルモハナッド, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Sou Shimizu, 比嘉佳基, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 抗腫瘍薬が誘導するROSは破骨細胞分化を促進する Xanthine oxidase阻害剤febuxostatの治療効果, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 148, Oct. 2020. (Keyword) Xanthine Oxidase(拮抗物質・阻害物質) / reactive oxygen species / 抗腫瘍剤(毒性・副作用) / 骨吸収(化学的誘発,薬物療法,実験的) / cell differentiation / osteoclast / 破骨細胞分化因子 / Febuxostat(治療的利用) / RAW264.7細胞 / マウス / animal
62.	Masahiro Oura, Shingen Nakamura, 堀太貴, Kimiko Sogabe, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Tomoko Kobayashi, Takeshi Oya and Masahiro Abe : 結節性紅斑と悪性腫瘍関連血球貪食症候群を惹起した骨髄異形成症候群の1例, The Japanese Journal of Clinical Hematology, Vol.61, No.10, 1542, Oct. 2020. (Keyword) 骨髄異形成症候群(合併症) 紅斑-結節性(病因) *血球貪食性リンパ組織球症(病因) ヒト中年(45~64) 男
63.	中村昌史, Hirokazu Miki, Masahiro Oura, 川田知代, 堀太貴, 村井純平, Ryohei Sumitani, Kimiko Sogabe, 高橋真美子, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Kumiko Kagawa, 菅崎幹樹, 徳永尚樹, Akishige Ikegame, 森下英理子 and Masahiro Abe : クロスミキシングテストの特徴的な所見が診断の契機となったプレカリクレイン欠乏症の1例, The Japanese Journal of Clinical Hematology, Vol.61, No.10, 1537-1538, Oct. 2020. (Keyword) Prekallikrein(欠損・欠乏) 血液凝固異常(診断) *血液凝固検査ヒト中年(45~64) 男
64.	堀大貴, Shingen Nakamura, Takeshi Harada, Ryohei Sumitani, 村井純平, 高松信敏, Fumitake Tezuka and Masahiro Abe : 若年で発症しアトピー性皮膚炎に合併した化膿性脊椎炎の1例, 第123回日本内科学会四国地方会, Jul. 2020.
65.	Takeshi Harada, Hirofumi Tenshin, Kotaro Tanimoto, Sou Shimizu and Masahiro Abe : MM cells overexpress SLAMF7 through HDAC1 and IRF4 upregulation, 第24回日本がん分子標的治療学会学術集会, Jun. 2020.
66.	山崎佳那子, 祖川麻衣子, Kazutoshi Murao, Yoshiaki Kubo, Masahiro Oura, Takeshi Harada, Shingen Nakamura and Kumiko Kagawa : 骨髄異形成症候群の患者に生じた晩発性皮膚ポルフィリン症の1例, The Nishinihon Journal of Dermatology, Vol.82, No.3, 238-239, Jun. 2020. (Keyword) 骨髄異形成症候群(合併症) Uroporphyrins(尿) ポルフィリン症-晩発性皮膚(合併症,診断) ヒト中年(45~64) 男
67.	村井純平, 堀太貴, 川田知代, Ryohei Sumitani, 宇高憲吾, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Kumiko Kagawa, Masahiro Abe, Hirokazu Miki, 桝田志保, Itsuro Endo and Seiji Fukumoto : 高ビタミンD血症による高Ca血症を来したホジキンリンパ腫の一例, Shikoku Acta Medica, Vol.76, No.1-2, 124, Apr. 2020. (Keyword) Calcitriol(毒性・副作用,血液) / Hodgkin病(合併症,薬物療法) / Vitamin D(毒性・副作用,血液) / 高カルシウム血症(化学的誘発) / 腫瘍多剤併用療法 / ヒト / 高齢者(65~79) / 男
68.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Mohannad Ashtar, Bat-Erdene Ariunzaya, Masami Iwasa, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1阻害は関節リウマチにおけるNLRP3インフラマソーム誘導性の炎症および骨破壊を抑制する, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, 190, Oct. 2019.
69.	Kotaro Tanimoto, Masahiro Hiasa, Akihiko Iwasa, Hirofumi Tenshin, Jumpei Teramachi, Mohannad Ashtar, Masami Iwasa, 小田明日香, 曾我部公子, Masahiro Oura, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 不動性骨吸収の亢進は骨髄内の骨髄腫進展を促進させる．, The Annual Meeting of the Japanese Society for Bone and Mineral Research Program & Abstracts, Oct. 2019.
70.	Takeshi Harada : The roles of HDAC isoforms and development of treatment with isoform-specific HDAC inhibitors in multiple myeloma, The 81th Annual Meeting of the Japanese Society of Hematology, Oct. 2019.
71.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Mohannad Ashtar, Ariunzaya Bat-Erdene, Masami Iwasa, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1阻害は関節リウマチにおけるNLRP3インフラマソーム誘導性の炎症および骨破壊を抑制する．, 第37回日本骨代謝学会学術集会, Oct. 2019.
72.	谷本幸太朗, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Mohannad Ashtar, Masami Iwasa, 小田明日香, Kimiko Sogabe, Masahiro Oura, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 不動性骨吸収の亢進は骨髄内の骨髄腫進展を促進させる, 第37回日本骨代謝学会学術集会, Oct. 2019.
73.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, 小田明日香, Kotaro Tanimoto, Soh Shimizu, Ashtar Mohannad, Takeshi Harada, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : NLRP3 inflammasome-mediated inflammation and osteoclastic bone resorption in rheumatoid arthritis : the therapeutic roles of TAK1 inhibition, 16th Meeting of Bone Biology Forum, Aug. 2019.
74.	安宅克博, Shingen Nakamura, Masahiro Oura, Kimiko Sogabe, Takeshi Harada, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Yasuhiko Nishioka and Masahiro Abe : 長期にわたる血小板減少が先行した芽球性形質細胞様樹状細胞腫瘍の1例, 第120回日本内科学会四国地方会, May 2019.
75.	Takeshi Harada, Oda Asuka, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Oura, Kimiko Sogabe, Masami Iwasa, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Teru Hideshima, Anderson C. Kenneth and Masahiro Abe : The novel therapeutic strategy targeting the HDAC1-IRF4-PIM2 pathway in myeloma cells, The 44th Annual Meeting of the Japanese Society of Myeloma, May 2019. (Keyword) Multiple myeloma / Class-I HDAC / IRF4 / Pim-2
76.	Jumpei Teramachi, Hirofumi Tenshin, Masahiro Hiasa, Oda Asuka, Bat-Erdene Ariunzaya, Takeshi Harada, Iwasa Masami, Shiroh Fujii, Kimiko Sogabe, Shingen Nakamura, Hirokazu Miki, Masahiro Oura, Kumiko Kagawa, Itsuro Endo, Toshio Matsumoto and Masahiro Abe : Mechanisms of TAK1 over-activation in myeloma cells and TAK1-mediated myeloma growth and bone destruction, 第80回日本血液学会学術集会, Oct. 2018.
77.	Takeshi Harada : Roles of HDAC1 and HDAC3 as therapeutic targets against myeloma cells, The 80th Annual Meeting of the Japanese Society of Hematology, Oct. 2018.
78.	Masami Iwasa, Takeshi Harada, Bat-Erdene Ariunzaya, 小田明日香, Kimiko Sogabe, Masahiro Oura, Jumpei Teramachi, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa and Masahiro Abe : HDAC阻害による骨髄腫細胞のIFN-γ-STAT1- PD-L1経路の増強効果, 第80回日本血液学会学術集会, Oct. 2018. (Keyword) Multiple myeloma
79.	Ashtar Mohannad, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Oda Asuka, Iwasa Masami, Takeshi Harada, Ariunzaya Erdene Bat, Kimiko Sogabe, Oura Masahiro, Shiroh Fujii, Kumiko Kagawa, Shingen Nakamura, Hirokazu Miki, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Roles of ROS in induction of bone disease and cancer treatment-induced bone loss in myeloma., The 80th Annual Meeting of the Japanese Society of Hematology, Oct. 2018.
80.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Mohannad Ashtar, Ariunzaya Bat-Erdene, Iwasa Masami, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Kimiko Sogabe, Oura Masahiro, Shiroh Fujii, Kumiko Kagawa, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Inverse regulation of c-FLIP-mediated survival in myeloma cells and osteoclasts by TRAIL., The 80th Annual Meeting of the Japanese Society of Hematology, Oct. 2018.
81.	Kotaro Tanimoto, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, Oda Asuka, Mohannad Ashtar, Ariunzaya Bat-Erdene, Iwasa Masami, Kimiko Sogabe, Oura Masahiro, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Impact of denervation-induced paralysis and mechanical unloading on tumor expansion in myeloma., The 80th Annual Meeting of the Japanese Society of Hematology, Oct. 2018.
82.	Masahiro Hiasa, Jumpei Teramachi, Hirofumi Tenshin, Kotaro Tanimoto, Ariunzaya Bat-Erdene, Mohannad Ashtar, Masami Iwasa, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Kimiko Sogabe, Oura Masahiro, Shiroh Fujii, Kumiko Kagawa, Oda Asuka, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : The effects of cathepsin K inhibition on osteocytes: its role in bone restoration in MM bone disease., The 80th Annual Meeting of the Japanese Society of Hematology, Oct. 2018.
83.	Masahiro Hiasa, Jumpei Teramachi, Hirofumi Tenshin, Kotaro Tanimoto, Mohannad Ashtar, Ariunzaya Bat-Erdene, Masami Iwasa, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : カテプシンK阻害による多発性骨髄腫骨病変部の骨量回復プロセスにおける骨細胞の役割．, 第36回日本骨代謝学会学術集会, Jul. 2018.
84.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Kotaro Tanimoto, Mohannad Ashtar, Ariunzaya Bat-Erdene, Masami Iwasa, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1阻害はTRAILによる破骨細胞活性化作用を遮断させると同時にTRAILの抗骨髄腫作用を増強する, 第36回日本骨代謝学会学術集会, Jul. 2018.
85.	Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, 小田明日香, Kotaro Tanimoto, Mohannad Ashtar, Ariunzaya Bat-Erdene, Masami Iwasa, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : TAK1による破骨細胞に対するTRAILの生存・細胞死シグナル制御機構．, 第4回日本骨免疫学会, Jun. 2018.
86.	Kotaro Tanimoto, Masahiro Hiasa, Hirofumi Tenshin, Jumpei Teramachi, 小田明日香, Mohannad Ashtar, Ariunzaya Bat-Erdene, Masami Iwasa, Kimiko Sogabe, 大浦雅弘, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : 神経切断による麻痺と免荷の骨髄腫の進展への影響．, 第4回日本骨免疫学会, Jun. 2018.
87.	Masami Iwasa, Takeshi Harada, Bat-Erdene Ariunzaya, 小田明日香, 前田悠作, 高橋真美子, Masahiro Oura, Jumpei Teramachi, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa and Masahiro Abe : Amplification of the IFN- γ -STAT1- PD-L1 pathway in myeloma cells by panobinostat, The 43rd Annual Meeting of the Japanese Society of Myeloma, May 2018. (Keyword) Multiple myeloma
88.	Takeshi Harada, Oda Asuka, Jumpei Teramachi, Bat-Erdene Ariunzaya, Iwasa Masami, Maeda Yusaku, Shingen Nakamura, Oura Masahiro, Shiroh Fujii, Hirokazu Miki, Kumiko Kagawa, Hideshima Teru, Anderson C. Kenneth and Masahiro Abe : HDAC1/3 inhibition disrupts the IRF4-Pim-2 pathway to induce effective myeloma cell death, The 43rd Annual Meeting of the Japanese Society of Myeloma, May 2018. (Keyword) Multiple myeloma / Class-I HDAC / IRF4 / Pim-2
89.	Jumpei Teramachi, Masahiro Hiasa, Oda Asuka, Hirofumi Tenshin, Ryota Amachi, Takeshi Harada, Shingen Nakamura, Masami Iwasa, Masahiro Oura, Yusaku Maeda, Shiroh Fujii, Kumiko Kagawa, Hirokazu Miki, Itsuro Endo, Toshio Matsumoto and Masahiro Abe : Disruption of myeloma cell-bone marrow interaction by TAK-1 inhibition, 第80回日本血液学会学術集会, Oct. 2017.
90.	Takeshi Harada, Ohguchi Hiroto, Grondin Yohann, Kikuchi Shohei, Sagawa Morihiko, Tai Yu-Tzu, Mazitschek Ralph, Hideshima Teru and Anderson C. Kenneth : HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications, The 79th Annual Meeting of the Japanese Society of Hematology, Oct. 2017. (Keyword) Multiple myeloma / HDAC3 / DNMT1
91.	Jumpei Teramachi, Hiroshi Mori, Yasuo Ochi, Ryota Amachi, Asuka Oda, Masahiro Hiasa, Takeshi Harada, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe : Potent induction of bone formation by anti-resorptive cathepsin K inhibitor in myeloma., The 77th Annual Meeting of the Japanese Society of Hematology, Oct. 2016.

Patent:

1.	Jumpei Teramachi, Michiyasu Nakao, Shigeki Sano, Masahiro Abe and Takeshi Harada : PIM2阻害剤, 2021- 14411 (Feb. 2021), 110000796 (Feb. 2021).

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

肺がんCT検診の性能向上のための遺伝情報と画像情報の融合研究 (Project/Area Number: 24K03308 )
骨形成環境による腫瘍排他的ニッチの分子機序の解明：新たながん治療戦略の可能性 (Project/Area Number: 24K02643 )
骨細胞保護によるがんの骨転移新規治療戦略の開発 (Project/Area Number: 23K27791 )
RNA編集酵素ADARが司る骨髄腫の進展様式と免疫逃避機構の解明 (Project/Area Number: 22K08455 )
Development of a novel treatment toward prevention of HTLV-1 transmission and ATL disease onset (Project/Area Number: 20K17402 )
Roles of HDAC1/3 effecting on metabolic shift in myeloma cells; Development of a novel treatment strategy targeting metabolic shift (Project/Area Number: 18K16118 )
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Associate Professor : Harada, Takeshi

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)