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• Locking Plate固定（PHILOS^TM）を行った上腕骨近位端骨折の治療成績

  親富祖 徹, 金谷 文則, 山口 浩, 大槻 健太, 当真 孝, 呉屋 五十八, 喜友名 翼, 森山 朝裕, 當銘 保則, 前原 博樹

  整形外科と災害外科 ( 西日本整形・災害外科学会 )  69 ( 2 ) 344 - 348   2020 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  <p>【目的】上腕骨近位部骨折用DePuy-Synthes社製PHILOS^TMプレート，（以下PHILOS）を用いて手術を行った上腕骨近位端骨折の治療成績を報告する．【対象および方法】PHILOSを用いて手術を行い6カ月以上経過観察可能であった65例65肩（男性16肩，女性49肩），年齢は20～87歳（平均64歳），骨折型（Neer分類）は2-part 27肩，3-part 31肩，4-part 7肩，観察期間6～64カ月（平均15カ月）であった．調査項目は自動肩関節可動域（屈曲・外旋・内旋：内旋のみJOAスコアに基づき点数化），骨癒合，合併症であり，年齢・骨折型と関節可動域に関する検討を行った．【結果】平均肩関節可動域は屈曲116°，外旋29°，内旋3.8点であった．合併症発生率は35％であった．年齢と屈曲・外旋可動域で負の相関関係を認めた．4-partでは屈曲可動域が有意に低下していた．【結語】PHILOS固定例では年齢と屈曲と外旋で負の相関関係を認め，4-part骨折では有意に屈曲が不良であった．</p>

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• Eribulin Suppressed Cisplatinum- and Doxorubicin-resistant Recurrent Lung Metastatic Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model.

  Kiyuna T, Tome Y, Miyake K, Murakami T, Oshiro H, Igarashi K, Kawaguchi K, Hsu J, Singh M, Li Y, Nelson S, Bouvet M, Singh SR, Kanaya F, Hoffman RM

  Anticancer research ( Anticancer Research )  39 ( 9 ) 4775 - 4779   2019.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  BACKGROUND: Osteosarcoma is a recalcitrant disease treated with surgery and intensive chemotherapy as standard. The 5-year survival rate of patients with relapsed and lung metastatic osteosarcoma is as low as 20%. MATERIALS AND METHODS: A 16-year-old patient developed left distal femoral high-grade osteosarcoma and underwent cisplatinum-based neoadjuvant chemotherapy and surgery. From the resected tumor, a patient-derived orthotopic xenograft (PDOX) model was established in the femur of nude mice. PDOX models were randomized into the following groups: untreated control, or treatment with doxorubicin (3 mg/kg, i.p., weekly for 14 days), sunitinib (40 mg/kg, oral gavage, daily for 14 days), pazopanib (100 mg/kg, oral gavage, daily for 14 days), temozolomide(25 mg/kg, oral gavage, daily for 14 days), and eribulin (1.5 mg/kg, i.p., daily for 14 days). Tumor volume and body weight were monitored twice a week. RESULTS: The osteosarcoma PDOX was resistant to doxorubicin, sunitinib, and pazopanib. In contrast, eribulin and temozolomide arrested tumor growth. CONCLUSION: This study demonstrated the utility of the PDOX model in allowing effective from non-effective drugs to be distinguished in a model in which the tumor was growing on the organ corresponding to that of the patient.

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• Oral Recombinant Methioninase Overcomes Colorectal-cancer Liver Metastasis Resistance to the Combination of 5-Fluorouracil and Oxaliplatinum in a Patient-derived Orthotopic Xenograft Mouse Model.

  Oshiro H, Tome Y, Kiyuna T, Yoon SN, Lwin TM, Han Q, Tan Y, Miyake K, Higuchi T, Sugisawa N, Katsuya Y, Park JH, Zang Z, Razmjooei S, Bouvet M, Clary B, Singh SR, Kanaya F, Nishida K, Hoffman RM

  Anticancer research ( Anticancer Research )  39 ( 9 ) 4667 - 4671   2019.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS: Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis.

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• Temozolomide targets and arrests a doxorubicin-resistant follicular dendritic-cell sarcoma patient-derived orthotopic xenograft mouse model.

  Oshiro H, Tome Y, Kiyuna T, Miyake K, Kawaguchi K, Higuchi T, Miyake M, Zang Z, Razmjooei S, Barangi M, Wangsiricharoen S, Nelson SD, Li Y, Bouvet M, Singh SR, Kanaya F, Hoffman RM

  Tissue & cell ( Tissue and Cell )  58   17 - 23   2019.06 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Follicular dendritic cell sarcoma (FDCS) is a very rare and highly recalcitrant disease. A patient's doxorubicin-resistant FDCS was previously established orthotopically on the right high thigh into the biceps femoris of mice to establish a patient-derived orthotopic xenograft (PDOX) model. The aim of the present manuscript was to identify an effective drug for this recalcitrant tumor. Here, we evaluated the efficacy of temozolomide (TMZ), trabectedin (TRAB) and pazopanib (PAZ) on the FDCS PDOX model. PDOX mouse models were randomized into five groups of eight to nine mice, respectively. Group 1, untreated control with PBS, i.p.; Group 2, treated with doxorubicin (DOX), 2.4 mg/kg, i.p., weekly for 3 weeks; Group 3, treated with PAZ, 50 mg/kg, oral gavage, daily for 3 weeks; Group 4, treated with TMZ, 25 mg/kg, oral gavage, daily for 3 weeks; Group 5, treated with TRAB, 0.15 mg/kg, i.v., weekly for 3 weeks. Body weight and tumor volume were assessed 2 times per week. TMZ arrested the FDCS PDOX model compared to the control group (p < 0.05). PAZ and TRAB did not have significant efficacy compared to the control group (p = 0.99, p = 0.69 respectively). The PDOX tumor was resistant to DOX (p= 0.99). as was the patient. The present study demonstrates that TMZ is effective for a PDOX model of FDCS established from a patient who failed DOX treatment, further demonstrating the power of PDOX to identify effective therapy including for tumors that failed first line therapy.

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• Detection of Metastasis in a Patient-derived Orthotopic Xenograft (PDOX) Model of Undifferentiated Pleomorphic Sarcoma with Red Fluorescent Protein.

  Oshiro H, Kiyuna T, Tome Y, Miyake K, Kawaguchi K, Higuchi T, Miyake M, Zhang Z, Razmjooei S, Barangi M, Wangsiricharoen S, Nelson SD, Li Y, Bouvet M, Singh SR, Kanaya F, Hoffman RM

  Anticancer research ( Anticancer Research )  39 ( 1 ) 81 - 85   2019.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  BACKGROUND/AIM: Undifferentiated pleomorphic sarcoma (UPS) is a common soft tissue sarcoma and highly recalcitrant. We have previously developed patient-derived orthotopic xenograft (PDOX) mouse models of UPS and other major sarcoma types. Unlike PDOX models of other cancer types, it has been difficult to demonstrate metastasis in the sarcoma PDOX models. MATERIALS AND METHODS: To visualize metastasis at high resolution in the UPS PDOX model, established tumor fragments were implanted in transgenic nude mice expressing red fluorescent protein (RFP) for one passage. The tumors acquired RFP-expressing stroma from transgenic host. UPS tumor with RFP stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. After six weeks of UPS tumor growth in the PDOX model, the primary tumor was imaged non-invasively and lung, liver, and spleen were resected and imaged ex-vivo in order to visualize the presence of RFP, with a FluorVivo® imaging system and FV1000® confocal laser microscope, respectively. RESULTS: The primary tumor was imaged non-invasively. Confocal microscopy visualized the presence of RFP in the lung and liver indicating metastases in these organs. This is the first report of metastasis in a sarcoma PDOX model. CONCLUSION: This study should prove very useful to screen for anti-metastatic drugs for the PDOX donor patients and to understand the metastatic process in sarcoma.

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• ヒト骨肉腫高肺転移株におけるmicroRNA発現の検討

  當銘 保則, 木村 浩明, 前原 博樹, 田中 一広, 上原 史成, 喜友名 翼, 土屋 弘行, Hoffman Robert, 金谷 文則

  日本整形外科学会雑誌 ( (公社)日本整形外科学会 )  88 ( 8 ) S1482 - S1482   2014.08

   

• In vivoセレクションによる骨肉腫肺転移株の樹立とインテグリン発現の検討

  當銘 保則, 前原 博樹, 木村 浩明, 田中 一広, 上原 史成, 土屋 弘行, 金谷 文則

  日本整形外科学会雑誌 ( (公社)日本整形外科学会 )  86 ( 8 ) S1310 - S1310   2012.08

   

• エキスタチンによるalpha(v)beta(3)integrinの分子標的治療はヒト骨肉腫細胞株の腫瘍増殖と転移を抑制する

  當銘 保則, 前原 博樹, 木村 浩明, 田中 一広, 上原 史成, 土屋 弘行, 金谷 文則

  日本整形外科学会雑誌 ( (公社)日本整形外科学会 )  86 ( 8 ) S1311 - S1311   2012.08

   

• エキスタチンによるαvβ3 Integrinの分子標的治療はヒト骨肉腫細胞株の腫瘍増殖と転移を抑制する

  當銘 保則, 前原 博樹, 木村 浩明, 田中 一広, 上原 史成, 土屋 弘行, Hoffman Robert M, 金谷 文則

  日本整形外科学会雑誌 ( (公社)日本整形外科学会 )  86 ( 6 ) S960 - S960   2012.06

   

• Clinical Outcome of Malignant Bone Tumor of the Femur Using KLS System

  TOME Yasunori, MAEHARA Hiroki, TANAKA Kazuhiro, KANAYA Fuminori

  整形外科と災害外科   59 ( 3 ) 476 - 480   2010.09

   

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Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Young Scientists(B)

  Project Year: 2015.04  -  2018.03 

  Direct: 3,000,000 (YEN)  Overheads: 900,000 (YEN)  Total: 3,900,000 (YEN)