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骨軟部腫瘍・骨代謝班

     
     
     
     
基礎研究・臨床研究の紹介
 
軟部腫瘍に対する新規分子標的薬オララツマブとAI療法の併用療法の可能性-患者由来組織同所移植モデルを用いた網羅的解析-
Cancer Lett 2019
オララツマブ (OLA) は軟部肉腫における初めての分子標的薬で,血小板由来成長因子受容体αを阻害し,細胞増殖を抑制する.標準薬ドキソルビシン(DOX)単剤と比較したphase-2臨床試験の結果で,OLAとDOXの併用療法が進行性軟部肉腫患者の予後を約2倍に延長したことで,2016年に欧米で迅速承認されたが,phase-3試験で,予後の改善を見出すことができず,2019年に承認が取り消された.しかし,OLAと他の化学療法との併用療法についての可能性は明らかにされていない.今回,標準治療レジメンであるAI (DOX + ifosfamide)療法とOLAとの併用療法の可能性について,患者由来組織同所移植モデルを用いて検討した.はじめに未分化多形肉腫患者の手術検体の一部をマウス皮下に移植した.増殖した腫瘍を分割してヌードマウスの大腿二頭筋内に移植し,マウスモデルを樹立した.このモデルをコントロール群,DOX群,OLA群,AI療法群, OLA+DOX群,OLA+AI群にランダムに振り分け,14日間の治療を行い,腫瘍サイズと体重を週2回測定した.治療後に腫瘍を切除し,Hematoxylin-Eosin (HE)染色とKi-67免疫組織化学染色で評価した.DOX群とOLA群を除く全ての群で, control群と比較し,有意に腫瘍の増殖が抑制されたが,AI群とOLA+DOX群の腫瘍増殖抑制効果は軽度であった.一方,OLA+AI群では腫瘍増殖が停止し,HE染色で広範な壊死を認め,Ki-67 陽性率は有意に減少した.全群で,有意な体重減少や大きな副作用はなかった.以上より,OLAとAI療法の併用療法は今後の臨床応用に期待できると考えた.
   
 
軟骨肉腫に対する非ステロイド性抗炎症薬ザルトプロフェンによるペルオキシゾーム増殖剤応答性受容体γとマトリックスメタロプロテアーゼ-2を介した抗腫瘍効果の解析
Cancer Med 2018
軟骨肉腫は2番目に多い原発性悪性骨腫瘍であるが,現在でも有効な化学療法や放射線治療がなく,手術以外の治療法がない.Peroxisome proliferator-activated receptor-γ(PPARγ)は脂肪細胞の分化に中心的な役割を果たす核内受容体型の転写因子で,近年,癌治療の新しい標的としても注目されている.我々は非ステロイド性鎮痛薬のザルトプロフェンが,PPARγを活性化することを初めて明らかにしました.本研究ではPPARγ活性化による治療の可能性が報告されている軟骨肉腫において,ザルトプロフェンのPPARγを標的とした抗腫瘍効果について解析した.まず,reporter gene assayを行い,ザルトプロフェンに強いPPARγ活性能を有することを確認し,western-blotやRT-PCRにより,ザルトプロフェンが軟骨肉腫細胞でPPARγの発現を濃度依存的に誘導することを見出した.続いて,proliferation assay,wound assay,invasion assay, zymographyなどのin vitro解析の結果から,ザルトプロフェンが軟骨肉腫細胞の増殖能や遊走浸潤能,MMP-2の発現を濃度依存的に抑制することを明らかにし,これらの作用がPPARγを介していることを遺伝子ノックダウン実験で確認した.最後に,鎮痛のため,ザルトプロフェンを長期内服していた頸椎軟骨肉腫の1例において,内服前後の手術検体を組織学的に評価し,ザルトプロフェン内服後の検体でPPARγの増強とMMP-2の減弱を認めることを確認した.軟骨肉腫の多くは緩徐に成長するため,局所の浸潤や遠隔転移さえ抑制できれば,腫瘍と共存したままでも,長期生存が見込める可能性がある.そのため,本研究で明らかにした,ザルトプロフェンによるPPARγやMMP-2を介した遊走浸潤抑制効果が,手術困難となった軟骨肉腫患者の新しい治療戦略になると考えた。
   
 
患者由来腫瘍組織同所移植モデルを用いた肉腫の個別化医療に向けた取り組み
Cell Cycle 2017
骨軟部肉腫はいわゆる希少がんであり症例数の少なさゆえに新規治療開発や新規薬剤開発に困難を伴います.より臨床を反映した動物モデルを作成することで研究開発を促進することができないかと考え,肉腫患者の腫瘍組織をマウスの同所に移植する動物モデルを作成し,従来の皮下移植モデルと比較検討行いました.
まず成人発症の大腿横紋筋肉腫患者より腫瘍組織の提供を受けて,マウスの皮下に移植しました.腫瘍が生着することを確認した後に,筋肉内移植モデルとして大腿四頭筋と大腿二頭筋内に腫瘍を移植,皮下モデルも作成し,腫瘍の動態につき評価しました.
移植後早期から筋肉内移植モデルは皮下移植モデルと比較し有意に腫瘍は増大し,移植後10週の段階ですべての腫瘍は長径20mmに達しました.また,腫瘍の辺縁切除後のマウスを経時的に観察したところ,皮下移植モデルから再発は認めませんでしたが,筋肉内移植モデルでは高確率で再発しました.切除した腫瘍を病理学的に評価したところ,筋肉内モデルにおいてのみ周囲筋組織への浸潤が認められました.
横紋筋肉腫を用いた患者由来腫瘍組織同所移植モデルは腫瘍増殖速度が速く,辺縁切除で局所再発を来たし,病理学的に周囲への明らかな浸潤傾向を認めるため,皮下移植モデルと比較しより悪性度が高く,患者臨床を反映した動物モデルであるといえます.
   
   
 
ヨード担持量の減衰評価と抗菌力との関係
Journal of Microbial & Biochemical Technology 2017
液ヨード担持インプラント表面に担持されたポピドンヨードの経時的な減衰変化と、ヨード量と抗菌力の評価について検討した。
担持されたヨード量が生体内での減衰量を評価するため、動物モデルによる評価を実施した。ウサギの皮下組織内、膝関節内、大腿骨内にそれぞれヨード担持インプラントを埋植し、表面に残存するヨード担持量を経時的に評価を行った。結果、365日経過後も約30%のポピドンヨードが試験片表面に残存していることが示された。
担持されたヨード量と抗菌力との関係性を評価するため、基準値に対して80%、50%、20%、0%(=酸化被膜)にヨード担持量を調節した試験片を作成し、黄色ブドウ球菌 (ATCC 25923)と大腸菌 (MG 1655)を播種し、培養した後の細菌数を経時的に評価した。その結果、20%のヨード担持量においても有意な細菌数の減少を認めた。
以上より、ヨード担持インプラントの抗菌力が長期に持続する可能性が示唆された。
     
     
 
 
骨肉腫に対するGSK3βを標的として新規分子標的治療薬の研究
Oncotarget 2016
骨肉腫は小児の長管骨骨幹端に発生することの多い、骨原発悪性腫瘍である。治療方法は抗がん剤と手術であるが、抗がん剤の副作用が強い症例や抗腫瘍効果が小さい症例などが存在する。そこで、骨肉腫に対するGSK3βを標的とした新規分子標的治療法の研究を行った。4種の骨肉腫細胞株(HOS、143B、MG-63、SaOS-2)と1種の骨芽細胞株(hFOB1.19)を用いた。GSK3β阻害薬はAR-A014418、SB-216763を使用した。それぞれの細胞株におけるGSK3β活性について調べ、阻害薬投与による細胞増殖抑制効果とアポトーシスの評価を行った。また、骨肉腫細胞株における阻害薬投与後のβ-cateninの変化を調べ、骨肉腫に対するGSK3β阻害薬の作用経路を検討した。In vivoでは骨肉腫細胞同所移植マウスにGSK3β阻害薬を腹腔内投与し、その抗腫瘍効果とメカニズムを検証した。活性型GSK3βの発現は、全ての骨肉腫細胞株において亢進していた(下図)。GSK3β阻害薬により全ての骨肉腫細胞の増殖抑制効果が認められ、アポトーシスが誘導された。また、GSK3β特異的siRNAを用いたRNA干渉試験でも阻害薬と同様の効果を得た。GSK3β阻害薬によりβ-cateninのリン酸化と分解が抑制され、β-cateninの核内移行と転写補因子活性が誘導された。骨肉腫細胞同所移植マウスに阻害薬を投与した結果、投与後2週間目から腫瘍増殖抑制効果が確認され、摘出腫瘍においてβ-cateninの核集積が認められた。この結果、GSK3β阻害薬による治療効果にはWnt/β-catenin経路が関係していると考えられた。
     
     
 
 
脂肪系腫瘍由来幹細胞と正常脂肪由来幹細胞の分化能の違い
Clinical Orthopaedic and Related Research 2017
間葉系幹細胞(MSC)においてp53蛋白は骨芽細胞分化や脂肪細胞分化を抑制する。多くの悪性腫瘍においてp53機能は低下しているため、悪性腫瘍の中のMSCにおいてもp53機能が低下しているならば骨芽細胞分化や脂肪細胞分化への誘導療法が有効である可能性があり、この仮説を異型脂肪腫様腫瘍/高分化型脂肪肉腫(ALT/WDL)を用いて検証しようと考えた。なぜなら、ほとんどのALT/WDLにおいてp53機能低下につながるMDM2遺伝子の増幅が認められるからである。同一個体からALT/WDL組織と正常脂肪組織を採取し、MSCを分離培養し、骨芽細胞分化能と脂肪細胞分化能を比較する。ALT/WDL患者6人から、腫瘍切除術の際に3mlの正常脂肪組織とALT組織を採取した。脂肪分化能はオイルレッドO染色後、抽出液の吸光度を測定して定量的に評価した。骨分化能はALP染色およびアリザリンレッドS染色後に特定色域面積を測定し半定量的に評価した。ALPは骨芽細胞分化初期の代謝に関連し、アリザリンレッドはカルシウム沈着と関連する。次に我々は骨芽細胞分化の差異が生じたメカニズムを、MDM2特異的阻害薬Nutlin-3の濃度を変えて加えることで分析した。脂肪分化能においては、我々の予想に反して、正常脂肪由来MSCにおいてより多くの脂肪滴が認められた。ただし抽出液の吸光度測定結果(正常脂肪対ALT/WDL)(±SD)は0.34 (± 0.13) 対 0.25 (± 0.10; p =0.22)で、有意差はなかった。対照的に、骨芽細胞分化能においては、ALT/WDL由来MSCでより高い分化能を認めた。ALP染色に基づいた分化能の値(正常脂肪対ALT/WDL)(±SD)は1.00 対 17 (±35.8; p =0.04)であった。しかしながら、アリザリンレッドS染色に基づいた分化能の値(正常脂肪対ALT/WDL)(±SD)は1.00対4.24(±4.75; p = 0.58)で、有意差を認めなかった。ALP染色に基づく骨芽細胞分化能の差異はMDM2特異的阻害薬Nutlin-3濃度が上昇するにつれて減少した。ALT/WDL由来MSCにおけるMDM2遺伝子の増幅がより高い骨芽細胞分化能をもたらしている可能性が示唆された。
     
     
 
業績
 
英語論文(2010~)
2020年
Eribulin Regresses a Doxorubicin-resistant Dedifferentiated Liposarcoma in a Patient-derived Orthotopic Xenograft Mouse Model
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Higuchi T, Yamamoto N, Hayashi K, Kimura H, Miwa S, Singh SR, Tsuchiya H, Hoffman RM 
Cancer Genomics Proteomics 17(4) 351-358 2020年7月

Risk Factors for Postoperative Deep Infection After Malignant Bone Tumor Surgery of the Extremities
Langit MB, Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K, Tada K, Higuchi T, Yonezawa H, Morinaga S, Araki Y, Asano Y, Tsuchiya H
Anticancer Res 40(6) 3551-3557 2020年6月

Recombinant Methioninase Combined With Tumor-targeting Salmonella typhimurium A1-R Induced Regression in a PDOX Mouse Model of Doxorubicin-resistant Dedifferentiated Liposarcoma
Igarashi K, Kawaguchi K, Zhao M, Han Q, Tan Y, Kiyuna T, Miyake K, Higuchi T, Nelson SD, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Singh SR, Tsuchiya H, Hoffman RM
Anticancer Res 40(5) 2515-2523 2020年5月

A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model
Igarashi K, Kawaguchi K, Yamamoto N, Hayashi K, Kimura H, Miwa S, Higuchi T, Taniguchi Y, Yonezawa H, Araki Y, Morinaga S, Misra S, Nelson SD, Dry SM, Li Y, Odani A, Singh SR, Tsuchiya H, Hoffman RM
Cancer Genomics Proteomics 17(3) 217-223 2020年5月

Cystic Extraskeletal Osteosarcoma: Three Case Reports and Review of the Literature
Araki Y, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Taniguchi Y, Yonezawa H, Morinaga S, Nojima T, Tsuchiya H
Mol Clin Oncol 12(5) 468-474 2020年5月

The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model
Higuchi T, Sugisawa N, Yamamoto J, Oshiro H, Han Q, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Tan Y, Kuchipudi S, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Cancer Chemother Pharmacol 85(2) 285-291 2020年2月

Pedicle Frozen Autograft-Prosthesis Composite Reconstructions for Malignant Bone Tumors of the Proximal Femur
Xu G, Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K, Higuchi T, Taniguchi Y, Araki Y, Yonezawa H, Morinaga S, Tsuchiya H 
BMC Musculoskelet Disord 6 21(1) 81 2020年2月

Glycogen Synthase Kinase 3β as a Potential Therapeutic Target in Synovial Sarcoma and Fibrosarcoma
Abe K, Yamamoto N, Domoto T, Bolidong D, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Inatani H, Aoki Y, Higuchi T, Taniguchi Y, Yonezawa H, Araki Y, Aiba H, Minamoto T, Tsuchiya H
Cancer Sci 111(2) 429-440 2020年2月

The Accuracy of Different FRAX Tools in Predicting Fracture Risk in Japan: A Comparison Study
Xu G, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Taniguchi Y, Araki Y, Yonezawa H, Morinaga S, Tsuchiya H
J Orthop Surg (Hong Kong) 28(2) 2309499020917276 2020年1月

PPARγ Agonist Pioglitazone in Combination With Cisplatinum Arrests a Chemotherapy-resistant Osteosarcoma PDOX Model
Higuchi T, Yamamoto J, Sugisawa N, Tashiro Y, Nishino H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Cancer Genomics Proteomics 17(1) 35-40 2020年1月

Patient-derived Orthotopic Xenograft Models of Sarcoma
Igarashi K, Kawaguchi K, Murakami T, Miyake K, Kiyuna T, Miyake M, Hiroshima Y, Higuchi T, Oshiro H, Nelson SD, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Singh SR, Tsuchiya H, Hoffman RM
Cancer Lett 28 469 332-339 2020年1月

2019年
Joint-preservation surgery for pediatric osteosarcoma of the knee joint
Takeuchi A, Yamamoto N, Hayashi K, Matsubara H, Miwa S, Igarashi K, Tsuchiya H
Cancer Metastasis Rev 38(4) 709-722 2019年12月

Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model.
Igarashi K, Kawaguchi K, Zhao M, Kiyuna T, Miyake K, Miyake M, Nelson SD, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Higuchi T, Singh SR, Tsuchiya H, Hoffman RM
Translational Oncology 13(2) 393-400 2019年12月

The process of bone regeneration from devitalization to revitalization after pedicle freezing with immunohistochemical and histological examination in rabbits.
Xu G, Yamamoto N, Nojima T, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Tsuchiya H
Cryobiology S0011-2240 (19) 30289-5 2019年12月

Combination of oral recombinant methioninase and decitabine arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma patient-derived orthotopic xenograft mouse model.
Higuchi T, Han Q, Miyake K, Oshiro H, Sugisawa N, Tan Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Biochemical and Biophysical Research Communications S0006-291X(19) 32344-7 2019年12月

Distribution of Solitary and Multiple Enchondromas of the Hand.
Miwa S, Okamoto H, Yamada S, Kawaguchi Y, Endo K, Aiba H, Hayashi K, Kimura H, Sekiya I, Otsuka T, Tsuchiya H
In Vivo 33(6) 2235-2240 2019年11-12月

Anti-tumor Effects of Cyclolinopeptide on Giant-cell Tumor of the Bone.
Taniguchi Y, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Higuchi T, Abe K, Yonezawa H, Araki Y, Morinaga S, Kamei J, Nugroho AE, Kaneda T, Morita H, Tsuchiya H
Anticancer Research 39(11) 6145-6153 2019年11月

A retrospective study of antibacterial iodine-coated implants for postoperative infection.
Shirai T, Tsuchiya H, Terauchi R, Tsuchida S, Mizoshiri N, Mori Y, Takeuchi A, Hayashi K, Yamamoto N, Ikoma K, Kubo T
Medicine (Baltimore) 98(45) e17932 2019年11月

Pioglitazone, an agonist of PPARγ, reverses doxorubicin-resistance in an osteosarcoma patient-derived orthotopic xenograft model by downregulating P-glycoprotein expression.
Higuchi T, Sugisawa N, Miyake K, Oshiro H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Kline Z, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Biomedicine & Pharmacotherapy 118 109356 2019年10月

Treatment of chordoma-where is it going?
Yamamoto N, Tsuchiya H
Journal of Spine Surgery 5(3) 387-389 2019年9月

Combination Treatment With Sorafenib and Everolimus Regresses a Doxorubicin-resistant Osteosarcoma in a PDOX Mouse Model.
Higuchi T, Sugisawa N, Miyake K, Oshiro H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Kline Z, Belt P, Chawla SP, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Anticancer Research 39(9) 4781-4786 2019年9月

Oral Recombinant Methioninase, Combined With Oral Caffeine and Injected Cisplatinum, Overcome Cisplatinum-Resistance and Regresses Patient-derived Orthotopic Xenograft Model of Osteosarcoma.
Higuchi T, Oshiro H, Miyake K, Sugisawa N, Han Q, Tan Y, Park J, Zhang Z, Razmjooei S, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Chawla SP, Singh SR, Tsuchiya H, Hoffman RM
Anticancer Research 39(9) 4653-4657 2019年9月

The Combination of Olaratumab with Doxorubicin and Cisplatinum Regresses a Chemotherapy-Resistant Osteosarcoma in a Patient-Derived Orthotopic Xenograft Mouse Model.
Higuchi T, Sugisawa N, Miyake K, Oshiro H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Translational Oncology 12(9) 1257-1263 2019年9月

Surgical treatment of chondroblastoma using extended intralesional curettage with phenol as a local adjuvant.
Zekry KM, Yamamoto N, Hayashi K, Takeuchi A, Araki Y, Alkhooly AZA, Abd-Elfattah AS, Fouly EH, Elsaid ANS, Tsuchiya H
Journal of Orthopaedic Surgery (Hong Kong) 27(3) 2309499019861031 2019年9月

Sorafenib and Palbociclib Combination Regresses a Cisplatinum-resistant Osteosarcoma in a PDOX Mouse Model.
Higuchi T, Sugisawa N, Miyake K, Oshiro H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Chawla SP, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Anticancer Research 39(8) 4079-4084 2019年8月

Caffeine citrate enhanced cisplatin antitumor effects in osteosarcoma and fibrosarcoma in vitro and in vivo.
Abe K, Yamamoto N, Hayashi K, Takeuchi A, Tsuchiya H
BMC Cancer 19(1) 689 2019年7月

C-arm cone-beam computed tomography-guided minimally invasive open excision of an osteoid osteoma undetectable on fluoroscopy: A case report.
Higuchi T, Yamamoto N, Hayashi K, Takeuchi A, Abe K, Taniguchi Y, Araki Y, Tsuchiya H
International Journal of Surgery Case Reports 61 14-19 2019年7月

Pazopanib regresses a doxorubicin-resistant synovial sarcoma in a patient-derived orthotopic xenograft mouse model.
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Higuchi T, Singh SR, Tsuchiya H, Hoffman RM
Tissue Cell 58 107-111 2019年6月

The combination of olaratumab with gemcitabine and docetaxel arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft mouse model.
Higuchi T, Miyake K, Sugisawa N, Oshiro H, Zhang Z, Razmjooei S, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Cancer Chemotherapy and Pharmacology 83(6) 1075-1082 2019年6月

Olaratumab combined with doxorubicin and ifosfamide overcomes individual doxorubicin and olaratumab resistance of an undifferentiated soft-tissue sarcoma in a PDOX mouse model.
Higuchi T, Miyake K, Sugisawa N, Oshiro H, Zhang Z, Razmjooei S, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Cancer Letters 451 122-127 2019年6月

Trabectedin and irinotecan combination regresses a cisplatinum-resistant osteosarcoma in a patient-derived orthotopic xenograft nude-mouse model.
Higuchi T, Miyake K, Oshiro H, Sugisawa N, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Chawla SP, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Biochemical and Biophysical Research Communications 513(2) 326-331 2019年5月

Progress in biological reconstruction and enhanced bone revitalization for bone defects.
Yamamoto N, Hayashi K, Tsuchiya H
Journal of Orthopaedic Science 24(3) 387-392 2019年5月

Successful treatment of pathologic femoral shaft fracture associated with large arteriovenous malformations using a 3-dimensional external fixator and teriparatide: a case report.
Takeuchi A, Matsubara H, Yamamoto N, Hayashi K, Miwa S, Igarashi K, Inatani H, Tsuchiya H
BMC Surgery 19(1) 35 2019年4月

Determining Patient Satisfaction and Treatment Desires in Patients With Musculoskeletal Sarcoma of the Knee After Joint-preservation Surgery Using a Questionnaire Survey.
Abe K, Yamamoto N, Hayashi K, Takeuchi A, Kato S, Miwa S, Igarashi K, Inatani H, Aoki YU, Higuchi T, Taniguchi Y, Tsuchiya H
Anticancer Research 39(4) 1965-1969 2019年4月

Satisfaction After Joint-preservation Surgery in Patients With Musculoskeletal Knee Sarcoma Based on Various Scores.
Abe K, Yamamoto N, Hayashi K, Takeuchi A, Kato S, Miwa S, Igarashi K, Inatani H, Aoki YU, Higuchi T, Taniguchi Y, Tsuchiya H
Anticancer Research 39(4) 1959-1964 2019年4月

Osimertinib Regresses an EGFR-Mutant Cisplatinum- Resistant Lung Adenocarcinoma Growing in the Brain in Nude Mice.
Higuchi T, Oshiro H, Zhang Z, Miyake K, Sugisawa N, Katsuya Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Zhao M, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM
Translational Oncology 12(4) 640-645 2019年4月

The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model.
Higuchi T, Kawaguchi K, Miyake K, Oshiro H, Zhang Z, Razmjooei S, Wangsiricharoen S, Igarashi K, Yamamoto N, Hayashi K, Kimura H, Miwa S, Nelson SD, Dry SM, Li Y, Chawla SP, Eilber FC, Singh SR, Tsuchiya H, Hoffman RM
Biomedicine & Pharmacotherapy 111 835-840 2019年3月

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: a study protocol.
Takeuchi A, Nomura A, Yamamoto N, Hayashi K, Igarashi K, Tandai S, Kawai A, Matsumine A, Miwa S, Nishida Y, Nakamura T, Terauchi R, Hoshi M, Kunisada T, Endo M, Yoshimura K, Murayama T, Tsuchiya H
BMC Musculoskeletal Disorders 20(1) 68 2019年2月

Current and Emerging Targets in Immunotherapy for Osteosarcoma.
Miwa S, Shirai T, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K, Tsuchiya H
Journal of Oncology 7035045 2019年1月

Risk factors for surgical site infection after malignant bone tumor resection and reconstruction.
Miwa S, Shirai T, Yamamoto N, Hayashi K, Takeuchi A, Tada K, Kajino Y, Higuchi T, Abe K, Aiba H, Taniguchi Y, Tsuchiya H
BMC Cancer 19(1) 33 2019年1月

Reconstruction of intercalary bone defect after resection of malignant bone tumor.
Zekry KM, Yamamoto N, Hayashi K, Takeuchi A, Alkhooly AZA, Abd-Elfattah AS, Elsaid ANS, Ahmed AR, Tsuchiya H
Journal of Orthopaedic Surgery (Hong Kong) 27(1) 2309499019832970 2019年1月

Therapeutic Targets for Bone and Soft-Tissue Sarcomas.
Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K, Tsuchiya H
International Journal of Molecular Sciences 20(1) pii E 170 2019年1月

2018年
Temozolomide regresses a doxorubicin-resistant undifferentiated spindle-cell sarcoma patient-derived orthotopic xenograft (PDOX): precision-oncology nude-mouse model matching the patient with effective therapy.
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
Journal of cellular biochemistry 119(8) 6598-6603 2018年8月
 
Imaging the interaction of αv integrin-GFP in osteosarcoma cells with RFP-expressing host stromal cells and tumor-scaffold collagen in the primary and metastatic tumor microenvironment.
Tome Y, Kiyuna T, Uehara F, Bouvet M, Tsuchiya H, Kanaya F, Hoffman RM
Journal of cellular biochemistry  2018年8月
 
Efficacy and Limitations of F-18-fluoro-2-deoxy-D-glucose Positron Emission Tomography to Differentiate Between Malignant and Benign Bone and Soft Tissue Tumors.
Miwa S, Mochizuki T, Yamamoto N, Shirai T, Hayashi K, Takeuchi A, Inatani H, Igarashi K, Higuchi T, Abe K, Taniguchi Y, Aiba H, Ikeda H, Tsuchiya H
Anticancer research 38(7) 4065-4072 2018年7月
 
Growth of epiphysis after epiphyseal-preservation surgery for childhood osteosarcoma around the knee joint.
Takeuchi A, Yamamoto N, Hayashi K, Matsubara H, Kimura H, Miwa S, Higuchi T, Abe K, Taniguchi Y, Tsuchiya H
BMC musculoskeletal disorders 19(1) 185 2018年6月
 
Factors Associated With Discharge Destination in Advanced Cancer Patients With Bone Metastasis in a Japanese Hospital.
Hayashi K, Yahata T, Muramoto R, Yamamoto N, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Aiba H, Araki Y, Tsuchiya H
Annals of rehabilitation medicine 42(3) 477-482 2018年6月
 
Mid- to long-term clinical outcome of giant cell tumor of bone treated with calcium phosphate cement following thorough curettage and phenolization.
Takeuchi A, Suwanpramote P, Yamamoto N, Shirai T, Hayashi K, Kimura H, Miwa S, Higuchi T, Abe K, Tsuchiya H
Journal of surgical oncology 117(6) 1232-1238 2018年5月
 
Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression.
Higuchi T, Takeuchi A, Munesue S, Yamamoto N, Hayashi K, Kimura H, Miwa S, Inatani H, Shimozaki S, Kato T, Aoki Y, Abe K, Taniguchi Y, Aiba H, Murakami H, Harashima A, Yamamoto Y, Tsuchiya H
Cancer medicine 7(5) 1944-1954 2018年5月
 
Calcium Phosphate Cement in the Surgical Management of Benign Bone Tumors.
Higuchi T, Yamamoto N, Hayashi K, Takeuchi A, Kimura H, Miwa S, Igarashi K, Abe K, Taniguchi Y, Aiba H, Tsuchiya H
Anticancer research 38(5) 3031-3035 2018年5月
 
Treatment outcomes of the simple bone cyst: A comparative study of 2 surgical techniques using artificial bone substitutes.
Higuchi T, Yamamoto N, Shirai T, Hayashi K, Takeuchi A, Kimura H, Miwa S, Abe K, Taniguchi Y, Tsuchiya H
Medicine 97(18) e0572 2018年5月
 
Growth of doxorubicin-resistant undifferentiated spindle-cell sarcoma PDOX is arrested by metabolic targeting with recombinant methioninase.
Igarashi K, Li S, Han Q, Tan Y, Kawaguchi K, Murakami T, Kiyuna T, Miyake K, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
Journal of cellular biochemistry 119(4) 3537-3544 2018年4月
 
Clinical outcomes of radio-hyperthermo-chemotherapy for soft tissue sarcoma compared to a soft tissue sarcoma registry in Japan: a retrospective matched-pair cohort study.
Aiba H, Yamada S, Mizutani J, Yamamoto N, Okamoto H, Hayashi K, Kimura H, Takeuchi A, Miwa S, Kawai A, Yoshimura K, Tsuchiya H, Otsuka T
Cancer medicine 7(4) 1560-1571 2018年4月
 
In vitro anticancer effects of a RAGE inhibitor discovered using a structure-based drug design system.
El-Far AHAM, Munesue S, Harashima A, Sato A, Shindo M, Nakajima S, Inada M, Tanaka M, Takeuchi A, Tsuchiya H, Yamamoto H, Shaheen HME, El-Sayed YS, Kawano S, Tanuma SI, Yamamoto Y
Oncology letters 15(4) 4627-4634 2018年4月
 
Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model.
Igarashi K, Kawaguchi K, Li S, Han Q, Tan Y, Gainor E, Kiyuna T, Miyake K, Miyake M, Higuchi T, Oshiro H, Singh AS, Eckardt MA, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
Oncotarget 9(27) 19263-19272 2018年4月
 
Recombinant methioninase in combination with doxorubicin (DOX) overcomes first-line DOX resistance in a patient-derived orthotopic xenograft nude-mouse model of undifferentiated spindle-cell sarcoma.
Igarashi K, Kawaguchi K, Li S, Han Q, Tan Y, Murakami T, Kiyuna T, Miyake K, Miyake M, Singh AS, Eckardt MA, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Singh SR, Eilber FC, Hoffman RM
Cancer letters 417 168-173 2018年3月
 
Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models.
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Singh AS, Eckardt MA, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Singh SR, Eilber FC, Hoffman RM
Biochemical and biophysical research communications 497(4) 1055-1061 2018年3月
 
Successful joint preservation of distal radius osteosarcoma by en bloc tumor excision and reconstruction using a tumor bearing frozen autograft: a case report.
Higuchi T, Yamamoto N, Hayashi K, Takeuchi A, Abe K, Taniguchi Y, Araki Y, Tada K, Tsuchiya H
BMC surgery 18(1) 12 2018年3月
 
Spontaneous shrinkage of solitary osteochondromas.
Aiba H, Yamada S, Yamamoto N, Hayashi K, Miwa S, Tsuchiya H, Otsuka T
Skeletal radiology 47(1) 61-68 2018年1月
 
The Efficacy of Wide Resection for Musculoskeletal Metastatic Lesions of Renal Cell Carcinoma.
Higuchi T, Yamamoto N, Hayashi K, Takeuchi A, Kato S, Miwa S, Abe K, Taniguchi Y, Aiba H, Tsuchiya H
Anticancer research 38(1) 577-582 2018年1月
 
Temozolomide combined with irinotecan regresses a cisplatinum-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) precision-oncology mouse model.
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
Oncotarget 9(8) 7774-7781 2018年1月
 
Tumor-targeting Salmonella typhimurium A1-R combined with recombinant methioninase and cisplatinum eradicates an osteosarcoma cisplatinum-resistant lung metastasis in a patient-derived orthotopic xenograft (PDOX) mouse model: decoy, trap and kill chemothe
Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Li S, Han Q, Tan Y, Zhao M, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM
Cell cycle (Georgetown, Tex.) 17(6) 801-809 2018年
 
Preoperative evaluation of the efficacy of radio-hyperthermo-chemotherapy for soft tissue sarcoma in a case series.
Aiba H, Yamada S, Mizutani J, Yamamoto N, Okamoto H, Hayashi K, Kimura H, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Araki Y, Tsuchiya H, Otsuka T
PloS one 13(4) e0195289 2018年
 
2017年
Yamamoto N, Tsuchiya H. Biological Reconstruction Using Liquid Nitrogen-Treated Tumor Bearing Bone. Osteosarcoma Biology, Behavior and Mechanisms. Kanya Honoki, Kurt Richard Weiss, ed. 1st ed. INTECH Zagreb 2017.

Hayashi K, Yamamoto N, Shirai T, Takeuchi A, Kimura H, Miwa S, Higuchi T, Abe K, Taniguchi Y, Aiba H, Kiyohara H, Imai R, Ikeda H, Tsuchiya H. Sequential histological findings and clinical response after carbon ion radiotherapy for unresectable sarcoma. Clinical and Translational Radiation Oncology. 2,41-45, 2017

Hayashi K, Niu X, Tang X, Singh VA, Asavamongkolkul A, Kawai A, Yamamoto N, Shirai T, Takeuchi A, Kimura A, Miwa S, Tsuchiya H. Experience of total scapular excision for musculoskeletal tumor and reconstruction in eastern Asian countries. Journal of Bone Oncology 9, 55-58, 2017

Miwa S, Nishida H, Tanzawa Y, Takeuchi A, Hayashi K, Yamamoto N, Mizukoshi E, Nakamoto Y, Kaneko S, Tsuchiya H. Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma. Cancer. 123(9):1576-1584,2017

Miwa S, Shirai T, Yamamoto N, Hayashi K, Takeuchi A, Tada K, Kajino Y, Inatani H, Higuchi T, Abe K, Taniguchi Y, Tsuchiya H. Risk factors for postoperative deep infection in bone tumors. PLoS One. 2017 Nov 9;12(11):e0187438. doi: 10.1371/journal.pone.0187438. eCollection 2017.

Igarashi K, Kawaguchi K, Kiyuna T, Murakami T, Miwa S, Nelson SD, Dry SM, Li Y, Singh AS, Kimura H, Hayashi K, Yamamoto N, Tsuchiya H, Eilber FC, Hoffman RM. Temozolomide combined with irinotecan caused regression in an adult pleomorphic rhabdomyosarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. Oncotarget. 2017 Mar 24;8(44):75874-75880. doi: 10.18632/oncotarget.16548. eCollection 2017 Sep 29.

Igarashi K, Kawaguchi K, Murakami T, Kiyuna T, Miyake K, Yamamoto N, Hayashi K, Kimura H, Nelson SD, Dry SM, Li Y, Singh AS, Miwa S, Odani A, Eilber FC, Tsuchiya H, Hoffman RM. A novel anionic-phosphate-platinum complex effectively targets an undifferentiated pleomorphic sarcoma better than cisplatinum and doxorubicin in a patient-derived orthotopic xenograft (PDOX). Oncotarget. 2017 Jun 28;8(38):63353-63359. doi: 10.18632/oncotarget.18806. eCollection 2017 Sep 8.

Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Murakami T, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Hoffman RM. Effective Metabolic Targeting of Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models with Recombinant Methioninase. Anticancer Res. 2017 Sep;37(9):4807-4812.

Igarashi K, Li S, Han Q, Tan Y, Kawaguchi K, Murakami T, Kiyuna T, Miyake K, Li Y, Nelson SD, Dry SM, Singh AS, Elliott IA, Russell TA, Eckardt MA, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM. Growth of doxorubicin-resistant undifferentiated spindle-cell sarcoma PDOX is arrested by metabolic targeting with recombinant methioninase. J Cell Biochem. 2017 Nov 16. doi: 10.1002/jcb.26527.

Igarashi K, Kawaguchi K, Kiyuna T, Murakami T, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Hoffman RM. Antimetastatic Efficacy of the Combination of Caffeine and Valproic Acid on an Orthotopic Human Osteosarcoma Cell Line Model in Nude Mice. Anticancer Res. 2017 Mar;37(3):1005-1011.

Igarashi K, Kawaguchi K, Kiyuna T, Murakami T, Miwa S, Nelson SD, Dry SM, Li Y, Singh AS, Kimura H, Hayashi K, Yamamoto N, Tsuchiya H, Eilber FC, Hoffman RM. Efficacy In Vitro of Caffeine and Valproic Acid on Patient-Derived Undifferentiated Pleomorphic Sarcoma and Rhabdomyosarcoma Cell Lines. Anticancer Res. 2017 Aug;37(8):4081-4084.

Igarashi K, Kawaguchi K, Murakami T, Kiyuna T, Miyake K, Singh AS, Nelson SD, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM. High Efficacy of Pazopanib on an Undifferentiated Spindle-Cell Sarcoma Resistant to First-Line Therapy Is Identified With a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model. J Cell Biochem. 2017 Sep;118(9):2739-2743. 

Igarashi K, Kawaguchi K, Murakami T, Kiyuna T, Miyake K, Nelson SD, Dry SM, Li Y, Yanagawa J, Russell TA, Singh AS, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Eilber FC, Hoffman RM. Intra-arterial administration of tumor-targeting Salmonella typhimurium A1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model. Cell Cycle. 2017 18;16(12):1164-1170. 

Inatani H, Yamamoto N, Hayashi K*, Kimura H, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Yamada S, Asai K, Otsuka T, Tsuchiya H. Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues? Clin Orthop Relat Res. 2017 Jun;475(6):1693-1701. 

Higuchi T, Yamamoto N, Nishida H, Hayashi K, Takeuchi A, Kimura H, Miwa S, Inatani H, Shimozaki S, Kato T, Aoki Y, Abe K, Taniguchi Y, Tsuchiya H. Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen. Int Orthop. 2017 41(10):2189-2197. 

Aiba H, Yamada S, Yamamoto N, Hayashi K, Miwa S, Tsuchiya H, Otsuka T. Spontaneous shrinkage of solitary osteochondromas. Skeletal Radiol. 2018 Jan;47(1):61-68. doi: 10.1007/s00256-017-2760-0. Epub 2017 Aug 19.

Rosario MS, Yamamoto N, Hayashi K, Takeuchi A, Kimura H, Miwa S, Higuchi T, Inatani H, Abe K, Taniguchi Y, Aiba H, Tsuchiya H. An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change. World J Surg Oncol. 2017 May 15;15(1):102. doi: 10.1186/s12957-017-1166-8.

Rosario M, Takeuchi A, Yamamoto N, Hayashi K, Miwa S, Higuchi T, Abe K, Taniguchi Y, Aiba H, Tanzawa Y, Murakami H, Tsuchiya H. Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone. Anticancer Res. 2017 Feb;37(2):749-754.

Zekry KM, Yamamoto N, Hayashi K, Takeuchi A, Higuchi T, Abe K, Taniguchi Y, Alkhooly AZAA, Abd-Elfattah AS, Fouly EH, Ahmed AR, Tsuchiya H. Intercalary frozen autograft for reconstruction of malignant bone and soft tissue tumours. Int Orthop. 2017 Jul;41(7):1481-1487. doi: 10.1007/s00264-017-3446-x. Epub 2017 Mar 25.

2016年
Kimura H, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Takeuchi A, Miwa S, Tsuchiya H. Clinical Outcome of Reconstruction Using Frozen Autograft for a Humeral Bone Tumor. Anticancer Res. 36: 6631-6635, 2016.

Takeuchi A, Yamamoto N, Hayashi K, Miwa S, Takahira M, Fukui K, Oikawa T, Tsuchiya H. Tenosynovial giant cell tumors in unusual locations detected by positron emission tomography imaging confused with malignant tumors: report of two cases. BMC Musculoskelet Disord. 2016 Apr 26;17:180. doi: 10.1186/s12891-016-1050-7.

Takeuchi A, Yamamoto N, Shirai T, Hayashi K, Miwa S, Munesue S, Yamamoto Y, Tsuchiya H. Clinical relevance of peroxisome proliferator-activated receptor-gamma expression in myxoid liposarcoma. BMC Cancer. 2016 Jul 11;16:442. doi: 10.1186/s12885-016-2524-6.

Takeuchi A, Tsuchiya H, Ishii T, Nishida Y, Abe S, Matsumine A, Kawai A, Yoshimura K, Ueda T. Clinical outcome of recurrent giant cell tumor of the extremity in the era before molecular target therapy: the Japanese Musculoskeletal Oncology Group study. BMC Musculoskelet Disord. 2016 Jul 22;17:306. doi: 10.1186/s12891-016-1163-z.

Miwa S, De Magalhaes N, Toneri M, Zhang Y, Cao W, Bouvet M, Tsuchiya H, Hoffman RM. Fluorescence-guided surgery of human prostate cancer experimental bone metastasis in nude mice using anti-CEA DyLight 650 for tumor illumination. J Orthop Res. 34: 559-565, 2016.

Miwa S, Toneri M, Igarashi K, Yano S, Kimura H, Hayashi K, Yamamoto N, Tsuchiya H, Hoffman RM. Real-time in vivo confocal fluorescence imaging of prostate cancer bone-marrow micrometastasis development at the cellular level in nude mice. J Cell Biochem. 117: 2533-2537, 2016.

Inatani H, Yamamoto N, Hayashi K, Kimura H, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Yamada S, Okamoto H, Otsuka T, Tsuchiya H. Surgical management of proximal fibular tumors: A report of 12 cases. J Bone Oncol. 5:163-166, 2016.

Shimozaki S, Yamamoto N, Domoto T, Nishida H, Hayashi K, Kimura H, Takeuchi A, Miwa S, Igarashi K, Kato T, Aoki Y, Higuchi T, Hirose M, Hoffman RM, Minamoto T, Hiroyuki T. Efficacy of glycogen synthase kinase-3β targeting against osteosarcoma via activation of β-catenin. Oncotarget. 7(47): 77038-51, 2016.

Shimozaki S, Inatani H, Numata H, Tsuchiya H. A Novel Technique for Calcaneal Avulsion Fracture: A Case Report. J Trauma Treatment. 5: 4, 2016.

Abe K, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Inatani H, Higuchi T, Taniguchi Y, Tsuchiya H. Balancing Prolonged Survival with QoL Using Low-dose Pazopanib Maintenance: A Comparison with the PALETTE Study. Anticancer Res. 36: 2893-2897, 2016.

Rosario MS, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Inatani H, Higuchi T, Tsuchiya H. A case of infected schwannoma mimicking malignant tumor. World J Surg Oncol. 14: 302, 2016.

Abdelaal AH, Yamamoto N, Hayashi K, Takeuchi A, Morsy AF, Miwa S, Kajino Y, Rubio DA, Tsuchiya H. Radiological assessment of the femoral bowing in Japanese population. SICOT J. 2:2, 2016.

Abdelaal AH, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Morsy AF, Kajino Y, Tsuchiya H. The linea aspera as a guide for femoral rotation after tumor resection: is it directly posterior? A technical note. J Orthop Traumatol. 17:255-9, 2016.

2015年
Hayashi K, Yamada S, Inatani H, Okamoto H, Takeuchi A, Nishida H, Yamamoto N, Tsuchiya H, Otsuka T. Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy. Anticancer Res. 35:493-8, 2015.

Kimura H, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Takeuchi A,  Igarashi K, Inatani H, Shimozaki S, Kato T, Aoki Y, Higuchi T, and Tsuchiya H. Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study. Cancer Med.4:333-41, 2015.

Takeuchi A, Yamamoto N, Shirai T, Nishida H, Hayashi K, Watanabe K, Miwa S, Tsuchiya H. Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report. BMC Surg. 15:124, 2015.

Miwa S, Yano S, Kimura H, Yamamoto M, Toneri M, Murakami T, Hayashi K, Yamamoto N, Fujiwara T, Tsuchiya H, Hoffman RM. Heterogeneous cell-cycle behavior in response to UVB irradiation by a population of single cancer cells visualized by time-lapse FUCCI imaging. Cell Cycle 14: 1932-7, 2015.

Miwa S, Yano S, Kimura H, Yamamoto M, Toneri M, Matsumoto Y, Uehara F, Hiroshima Y, Murakami T, Hayashi K, Yamamoto N, Bouvet M, Fujiwara T, Tsuchiya H, Hoffman RM. Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging. Cell Cycle 14: 621-9, 2015.

Miwa S, Yokogawa A, Kobayashi T, Nishimura T, Igarashi K, Inatani H, Tsuchiya. Risk factors of recurrent lumbar disc herniation: A single center study and review of the literature J Spinal Disord Tech 28: E265-9, 2015.

Miwa S, Yano S, Yamamoto M, Matsumoto Y, Uehara F, Toneri M, Murakami T, Kimura H, Hayashi K, Yamamoto N, Efimova EV Tsuchiya H, Hoffman RM. Real-time fluorescence imaging of the DNA damage repair response during mitosis. J Cell Biochem 116: 661-6, 2015.

Abe K, Takeuchi A, Yamamoto N, Hayashi K, Tada K, Miwa S, Inatani H, Aoki Y, Higuchi T, Tsuchiya H. Symptomatic small schwannoma is a risk factor for surgical complications and correlates with difficulty of enucleation. SprungerPlus 4: 751, 2015.

Subhadrabandhu S, Takeuchi A, Yamamoto N, Shirai T, Nishida H, Hayashi K, Miwa S, Tsuchiya H. Frozen Autograft-Prosthesis Composite Reconstruction in Malignant Bone Tumors. Orthopedics. 38:e911-8, 2015.

2014年
Hayashi K,Iwata S,Ogose A,Kawai A,Ueda T,Otsuka T,Tsuchiya H. Factors that influence functional outcome after total or subtotal scapulectomy: Japanese usculoskeletal Oncology Group (JMOG) study. PLoS One. 6: e100119,2014.

Kimura H,Yamamoto N,Nishida H,Hayashi K,Takeuchi A,Nojima T,Ikeda H,Sawada-Kitamura S,Tsuchiya H.: Synovial sarcoma in knee joint,mimicking low-grade sarcoma confirmed by molecular detection of SYT gene split. Anticancer Res. 26: 3105-11,2014.

Takeuchi A, Lewis VO, Satcher RL, Moon BS, Lin PP: What are the factors that affect survival and relapse after local recurrence of osteosarcoma? Clin Orthop Relat Res. 472: 3188-95, 2014.

Miwa S,Zhang Y,Baek KE,Uehara F,Yano S,Yamamoto M,Hiroshima Y,Matsumoto Y,Kimura H,Hayashi K, Yamamoto N,Tsuchiya H,Bouvet M,Hoffman RM,Zhao M: Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R. Oncotarget. 5: 12849-61,2014.

Miwa S,Takeuchi A,Shirai T,Yamamoto N,Hayashi K,Nishida H,Kimura H,Igarashi K,Tsuchiya H: Outcomes and complications of reconstruction using tumour-bearing frozen autografts in patients with metastatic bone tumors. Anticancer Res. 34: 5569-77,2014.

Miwa S,Yano S,Zhang Y,Matsumoto Y,Uehara F,Yamamoto M,Hiroshima Y,Kimura H,Hayashi K,Yamamoto N, Bouvet M,Tsuchiya H,Hoffman RM,Zhao M: Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice. Oncotarget. 5: 7119-25,2014.

Miwa S,Hiroshima Y,Yano S,Zhang Y,Matsumoto Y,Uehara F,Yamamoto M,Kimura H,Hayashi K,Bouvet M, Tsuchiya H,Hoffman RM. Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude-mouse model. J Orthop Res. 32: 1596-601,2014.

Miwa S,Matsumoto Y,Hiroshima Y,Yano S,Uehara F,Yamamoto M,Zhang Y,Kimura H,Hayashi K,Yamamoto N, Bouvet M,Sugimoto N,Tsuchiya H,Hoffman RM: Fluorescence guided-surgery of prostate cancer bone metastasis. J Surg Res. 192: 124-33,2014.

Igarashi K,Yamamoto N,Shirai T,Hayashi K,Nishida H,Kimura H,Takeuchi A,Tsuchiya H: The long-term outcome following the use of frozen autograft treated with liquid nitrogen in the management of bone and soft-tissue sarcomas. Bone Joint J(B). 4: 555-61,2014.

Igarashi K,Yamamoto N,Shirai T,Nishida H,Hayashi K,Tanzawa Y,Kimura H,Takeuchi A,Miwa S,Inatani H, Shimozaki S,Kato T,Tsuchiya H: Late recurrence of osteosarcoma: a report of two cases. J Orthop Surg (Hong Kong). 3: 415-9,2014.

Shimozaki S,Yamamoto N,Shirai T,Nishida H,Hayashi K,Tanzawa Y,Kimura H,Takeuchi A,Igarashi K,Inatani H, Kato T,Tsuchiya H: Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities. J Orthop Sci. 1: 156-63,2014.

2013年
Yamamoto N, Tsuchiya H. Chemotherapy for osteosarcoma - where does it come from? What is it? Where is it going? Expert Opin Pharmacother. 14 :2183-93, 2013

Takeuchi A, Yamamoto N, Nishida H, Kimura H, Ikeda H, Tsuchiya H. Complete necrosis of a giant cell tumor with high expression of PPARγ: a case report. Anticancer Res. 2013 May;33(5):2169-74.

Takeuchi A, Yamamoto Y, Munesue S, Harashima A, Watanabe T, Yonekura H, Yamamoto H, Tsuchiya H. Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells. Cancer Sci. 2013 Jun;104(6):740-9.

Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas and their morphological mimics.
Kimura H, Dobashi Y, Nojima T, Nakamura H, Yamamoto N, Tsuchiya H, Ikeda H, Sawada-Kitamura S, Oyama T, Ooi A.
Int J Clin Exp Pathol. 2013 Jun 15;6(7):1306-16.

2012年
Tsuchiya H, Shirai T, Nishida H, Murakami H, Kabata T, Yamamoto N, Watanabe K, Nakase J: Innovative antimicrobial coating of titanium implants with iodine. J Orthop Sci. 5: 595-604. 2012

Yamamoto N, Hayashi K, Yamauchi K, Takeuchi A, Kimura H, Igarashi K, Hoffman RM, Tsuchiya H: In vitro and in vivo models for real-time or time course tumor cell imaging. Int J Mol Med. 30: S6, 2012.

Yamamoto N, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Inatani H, Shimozaki S, Kitamura S, Tsuchiya H: Treatment strategies for well-differentiated liposarcomas and therapeutic outcomes. Anticancer Res. 32: 1821-5, 2012.

Yamamoto N, Inatani H, Shirai T, Nishida H, Hayashi K, Kimura H, Takeuchi A, Igarashi K, Shimozaki S, Kato T, Tsuchiya H: Histological study on liquid nitrogen-treated tumor-bearing bone of the proximal femur excised eight years after transplantation. Low Temp Med. 38: 5-8, 2012.

Kimura H, Tome Y, Momiyama M, Hayashi K, Tsuchiya H, Bouvet M, Hoffman RM.: Imaging the inhibition by anti-β1 integrin antibody of lung seeding of single osteosarcoma cells in live mice. Int J Cancer. 131: 2027-33, 2012.

Miwa S, Taki J, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Ooi A, Tsuchiya H: A novel combined radiological method for evaluation of the response to chemotherapy for primary bone sarcoma. Journal of Surgical Oncology 106: 273-9, 2012.

Miwa S, Sugimoto N, Yamamoto N, Shirai T, Nishida H, Hayashi K, Kimura H, Takeuchi A, Igarashi K, Yachie A, Tsuchiya H: Caffeine induces apoptosis by inhibiting Akt/mTOR/S6K, NF-κB and MAPK pathways in osteosarcoma cell. Anticancer Research 32: 3643-9, 2012.

Miwa S, Nishida H, Tanzawa Y, Takeuchi A, Yamamoto N, Hayashi K, Kimura H, Tsuchiya H: TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. PLoS ONE 7: e52926

2011年
Hayashi K, Karita M, Yamamoto N, Shirai T, Nishida H, Takeuchi A, Kimura H, Miwa S, Tsuchiya H.
Functional outcomes after total scapulectomy for malignant bone or soft tissue tumors in the shoulder girdle.
Int J Clin Oncol. 12: [Epub ahead of print], 2011. PubMed PMID: 21480004.

Tsuchiya H, Takeuchi A, Yamamoto N, Shirai T, Hayashi K, Nishida H, Tomita K.
High-grade undifferentiated pleomorphic sarcoma of pelvis treated with curettage and bone graft after complete remission following caffeine-potentiated chemotherapy.
J Orthop Sci. Apr 2: [Epub ahead of print], 2011. PubMed PMID: 21461725.

Nishida H, Yamamoto N, Tanzawa Y, Tsuchiya H.
Cryoimmunology for malignant bone and soft-tissue tumors.
Int J Clin Oncol. 16(2):109-17, 2011. PubMed PMID: 21400111.

Tsuchiya H.
Basic science and clinical frontiers of sarcoma treatment.
Int J Clin Oncol. 16(2):82-3, 2011. PubMed PMID: 21387159.

Yamamoto N, Tsuchiya H, Hoffman RM.
Tumor imaging with multicolor fluorescent protein expression.
Int J Clin Oncol. 16(2):84-91, 2011. PubMed PMID: 21347627.

Tanzawa Y, Tsuchiya H, Shirai T, Nishida H, Hayashi K, Takeuchi A, Kawahara M, Tomita K.
Potentiation of the antitumor effect of calcium phosphate cement containing anticancer drug and caffeine on rat osteosarcoma.
J Orthop Sci. 16:77-84, 2011.

Miwa S, Shirai T, Taki J, Sumiya H, Nishida H, Hayashi K, Takeuchi A, Ooi A, Tsuchiya H.
Use of (99m)Tc-MIBI scintigraphy in the evaluation of the response to chemotherapy for osteosarcoma: comparison with (201)Tl scintigraphy and angiography. Int J Clin Oncol. 18: , 2011.

Takeuchi A, Tsuchiya H, Niu X, Ueda T, Jeon DG, Wang EH, Asavamongkolkul A, Kusuzaki K, Sakayama K, Kang YK.
The prognostic factors of recurrent GCT: a cooperative study by the Eastern Asian Musculoskeletal Oncology Group.
J Orthop Sci. 16:196-202, 2011.