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Igarashi, Kentaro ; Kawaguchi, Kei ; Kiyuna, Tasuku ; Miyake, Kentaro ; Miyake, Masuyo ; Li, Yunfeng ; Nelson, Scott D. ; Dry, Sarah M. ; Singh, Arun S. ; Elliott, Irmina A. ; Russell, Tara A. ; Eckardt, Mark A. ; Yamamoto, Norio ; Hayashi, Katsuhiro ; Kimura, Hiroaki ; Miwa, Shinji ; Tsuchiya, Hiroyuki ; Eilber, Fritz C. ; Hoffman, Robert M. ; 五十嵐, 健太郎 ; 山本, 憲男 ; 林, 克洋 ; 三輪, 真嗣 ; 土屋, 弘行
出版情報: Oncotarget.  9  pp.7774-7781,  2018.  Impact Journals LLC
URL: http://hdl.handle.net/2297/00050489
概要: 金沢大学医薬保健研究域医学系<br />Relapsed osteosarcoma is a recalcitrant tumor. A patient's cisplatinum (CDDP)- resistant relapsed os teosarcoma lung metastasis was previously established orthotopically in the distal femur of mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the PDOX models were randomized into the following groups when tumor volume reached 100 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly, for 2 weeks); gemcitabine (GEM) (100 mg/kg, i.p., weekly, for 2 weeks) combined with docetaxel (DOC) (20 mg/kg, i.p., once); temozolomide (TEM) (25 mg/kg, p.o., daily, for 2 weeks) combined with irinotecan (IRN) (4 mg/kg i.p., daily for 2 weeks). Tumor size and body weight were measured with calipers and a digital balance twice a week. After 2 weeks, all treatments significantly inhibited tumor growth except CDDP compared to the untreated control: CDDP: p = 0.093; GEM+DOC: p = 0.0002, TEM+IRN: p < 0.0001. TEM combined with IRN was significantly more effective than either CDDP (p = 0.0001) or GEM combined with DOC (p = 0.0003) and significantly regressed the tumor volume compared to day 0 (p = 0.003). Thus the PDOX model precisely identified the combination of TEM-IRN that could regress the CDDP-resistant relapsed metastatic osteosarcoma PDOX. © Igarashi et al. 続きを見る
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Higuchi, Takashi ; Takeuchi, Akihiko ; Munesue, Seiichi ; Yamamoto, Norio ; Hayashi, Katsuhiro ; Kimura, Hiroaki ; Miwa, Shinji ; Inaki, Hiroyuki ; Shimozaki, Shingo ; Kato, Takashi ; Aoki, Yu ; Abe, Kensaku ; Taniguchi, Yuta ; Aiba, Hisaki ; Murakami, Hideki ; Harashima, Ai ; Yamamoto, Yasuhiko ; Tsuchiya, Hiroyuki ; 武内 , 章彦 ; 棟居, 聖一 ; 山本, 憲男 ; 林 , 克洋 ; 三輪, 真嗣 ; 谷口, 裕太 ; 原島, 愛 ; 山本, 靖彦 ; 土屋, 弘行
出版情報: Cancer Medicine.  7  pp.1944-1954,  2018-05.  Wiley-Blackwell
URL: http://hdl.handle.net/2297/00053846
概要: 金沢大学医薬保健研究域医学系<br />Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemoth erapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti-inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti-tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ-responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase-2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.<br />29573200 続きを見る
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Higuchi, Takashi ; Yamamoto, Norio ; Nishida, Hideji ; Hayashi, Katsuhiro ; Takeuchi, Akihiko ; Kimura, Hiroaki ; Miwa, Shinji ; Inatani, Hiroyuki ; Shimozaki, Shingo ; Kato, Takashi ; Aoki, Yu ; Abe, Kensaku ; Taniguchi, Yuta ; Tsuchiya, Hiroyuki
出版情報: International Orthopaedics.  41  pp.2189-2197,  2017-10-01.  Springer Verlag
URL: http://hdl.handle.net/2297/48591
概要: Purpose: To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perfo rm epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma. Methods: Between 2006 and 2014, we performed joint-preserving surgery (12 with the free-freezing method and six with the pedicle freezing method) to treat 18 cases of osteosarcoma (12 distal femurs and six proximal tibias) in patients who had achieved a good response to neoadjuvant chemotherapy. Results: Among the 18 patients (nine boys and nine girls) who had a mean age of 11.6 years, 13 remained continuously disease-free, three showed no evidence of disease, one was alive with the disease, and one died from the disease. Functional outcomes were assessed as excellent in 15 patients and poor in three, with a mean follow-up period of 46.1 months. The mean Musculoskeletal Tumour Society (MSTS) score was 90.2%. Except for one patient who underwent amputation, all patients could bend their knee through >90° flexion, and nine achieved full ROM. All but two patients could walk without aid, and 11 were able to run normally throughout the follow-up period. No intraoperative complications were observed, such as surrounding soft-tissue damage, neurovascular injury, or recurrence from frozen bone. Conclusions: Joint-preserving reconstruction using frozen autografts yielded excellent function in patients with osteosarcoma. © 2017 The Author(s)<br />in Press / Embargo Period 12 months 続きを見る
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Hayashi, Katsuhiro ; Niu, Xiaohui ; Tang, Xiaodong ; Singh, Vivek Ajit ; Asavamongkolkul, Apichat ; Kawai, Akira ; Yamamoto, Norio ; Shirai, Toshiharu ; Takeuchi, Akihiko ; Kimura, Hiroaki ; Miwa, Shinji ; Tsuchiya, Hiroyuki ; 林, 克洋 ; 山本, 憲男 ; 白井, 寿治 ; 武内, 章彦 ; 木村, 浩彰 ; 三輪, 真嗣 ; 土屋, 弘行
出版情報: Journal of Bone Oncology.  9  pp.55-58,  2017-11-01.  Elsevier
URL: http://hdl.handle.net/2297/46760
概要: Total scapulectomy and reconstruction has been performed for scapular tumor, however, most of the reconstruction methods have resulted in poor functional outcomes and there is still room for improvement. Most of the reports of reconstruction after scapulectomy are from a single institution. In the present study, we investigated functional outcomes after total scapulectomy in a multicenter study in The Eastern Asian Musculoskeletal Oncology Group (EAMOG). Thirty-three patients who underwent total scapulectomy were registered at EAMOG affiliated hospitals. The patients were separated into no reconstruction group (n=8), humeral suspension group (n=15) and prosthesis group (n=10). Functional outcome was assessed by the Enneking score. One-way ANOVA was used to compare parameters between the patient groups. Complications included five local recurrences, one superficial infection, one dislocation and one clavicle protrusion. The average follow-up period was 43.5. months. The average active flexion range was 45.8° (0-120°), and 37.1° in abduction (0-120°). The mean total functional score was 22.9 out of 30 (15-29), which is a satisfactory score following resection of the shoulder girdle. There were significant differences in reconstruction methods for active range of motion. Bony reconstruction provided better range of motion in this study. There was a variety of reconstruction methods after scapulectomy in the eastern Asian countries. Although better functional score was obtained using scapular prosthesis or recycled bone and prosthesis composite grafting, postoperative function is still lower than preoperative function. Modified designed prosthesis with or without combination of recycle bone or allograft would restore the lost shoulder function in the future. © 2016 The Authors.<br />Embargo Period 12 months 続きを見る
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Miwa, Shinji ; Shirai, Toshiharu ; Yamamoto, Norio ; Hayashi, Katsuhiro ; Takeuchi, Akihiko ; Tada, Kaoru ; Kajino, Yoshitomo ; Inatani, Hiroyuki ; Higuchi, Takashi ; Abe, Kensaku ; Taniguchi, Yuta ; Tsuchiya, Hiroyuki ; 三輪, 真嗣 ; 白井, 寿治 ; 山本, 憲男 ; 林, 克洋 ; 武内, 章彦 ; 多田, 薫 ; 樋口, 貴史 ; 阿部, 健作 ; 土屋, 弘行
出版情報: PLoS ONE.  12  pp.e0187438-,  2017-11-01.  Public Library of Science
URL: http://hdl.handle.net/2297/00049635
概要: 金沢大学医薬保健研究域医学系<br />Background: Postoperative deep infection after bone tumor surgery remains a serious complication. Al though there are numerous reports about risk factors for postoperative deep infection in general surgery, there is only a small number of reports about those for bone tumor surgery. This retrospective study aimed to identify risk factors for postoperative deep infection after bone tumor resection. Methods: We reviewed data of 681 patients (844 bone tumors) who underwent surgery. Associations between variables, including age, recurrent tumor, pathological fracture, surgical site (pelvis/other), chemotherapy, biological reconstruction, augmentation of artificial bone or bone cement, the use of an implant, intraoperative blood loss, operative time, additional surgery for complications, and postoperative deep infection were evaluated. Results: The rate of postoperative deep infection was 3.2% (27/844 tumors). A pelvic tumor (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.0–11.3) and use of an implant (OR: 9.3, 95% CI: 1.9–45.5) were associated with an increased risk of deep infection. Conclusions: This retrospective study showed that pelvic tumor and use of an implant were independent risk factors for deep infection. This information will help surgeons prepare an adequate surgical plan for patients with bone tumors. © 2017 Miwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 続きを見る
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Tanzawa, Yoshikazu ; Tsuchiya, Hiroyuki ; Shirai, Toshiharu ; Hayashi, Katsuhiro ; Zen, Yoh ; Tomita, Katsuro
出版情報: Journal of Orthopaedic Science.  14  pp.761-768,  2009-11-01.  Springer Verlag (Germany) / 日本整形外科学会 = the Japanese Orthopaedic Association
URL: http://hdl.handle.net/2297/20357
概要: 金沢大学医薬保健研究域医学系<br />Background: Several oncological sterilization methods involving autoclaving, irradiation, or pasteur ization have been developed for limb reconstruction of large bone defects following tumor excision. Studies involving histological examinations of these autografts have all found that osteogenesis occurs slowly. We have used frozen autografts treated by liquid nitrogen for limb reconstruction and have achieved excellent results for bone union. To determine if frozen autografts exhibit early bone remodeling, we investigated the repair processes of the frozen bones. Methods: We analyzed frozen autografts treated by liquid nitrogen, retrieved at a mean of 19.1 months (2-75 months) after implantation because of complications or local tumor recurrence. The specimens were obtained from six patients with a mean age of 36.2 years (8-68 years). The six grafts comprised three osteoarticular grafts, two intercalary grafts, and one joint graft. We histologically reviewed the autograft-containing sections for tumor cell necrosis, evidence of cortical repair, the cortical junction, and joint cartilage. Results: Tumor cells were completely eradicated from the frozen bone in all cases. In a specimen retrieved 5 months after implantation, a small area of the bone showed active osteocytes and osteoblasts. In three cases retrieved more than 1 year after implantation, osteocytes and osteoblasts were observed in broad portions of the frozen bones, indicating the onset of osteogenesis in the frozen bone at an early stage. The cortical host-graft junction showed incorporation along with continuity of bone trabeculae. In addition, we were able to fi nd normal chondrocytes on the articular surface. Conclusions: The frozen bone specimens in this study thus showed evidence of newly formed bone and earlier osteogenesis than has been previously reported. Our results suggest that frozen autografts may be considered one of the most useful recycled materials for biological reconstruction. © 2009 The Japanese Orthopaedic Association. 続きを見る
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Tsuchiya, Hiroyuki ; Takeuchi, Akihiko ; Yamamoto, Norio ; Shirai, Toshiharu ; Hayashi, Katsuhiro ; Nishida, Hideji ; Tomita, Katsuro
出版情報: Journal of Orthopaedic Science.  16  pp.476-481,  2011-07-01.  Springer Verlag
URL: http://hdl.handle.net/2297/27649
概要: 金沢大学医薬保健研究域医学系
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Tsuchiya, Hiroyuki ; Takeuchi, Akihiko ; Yamamoto, Norio ; Shirai, Toshiharu ; Hayashi, Katsuhiro ; Nishida, Hideji ; Tomita, Katsuro
出版情報: Journal of Orthopaedic Science.  16  pp.476-481,  2011-07-01.  Springer Verlag (Germany) / The Japanese Orthopaedic Association
URL: http://hdl.handle.net/2297/29485
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Yamamoto, Norio ; Hayashi, Katsuhiro ; Tanzawa, Yoshikazu ; Kimura, Hiroaki ; Takeuchi, Akihiko ; Igarashi, Kentaro ; Inatani, Hiroyuki ; Shimozaki, Shingo ; Kitamura, Seiko ; Tsuchiya, Hiroyuki
出版情報: Anticancer Research.  32  pp.1821-1826,  2012-05-01.  Slack
URL: http://hdl.handle.net/2297/31969
概要: This study examined 45 patients with welldifferentiated liposarcoma who were surgically treated at our hospital (initial surgery in 41 patients and reoperation in 4). Only one patient had recurrence among patients who underwent initial surgery, and the recurrence was localised in the retroperitoneal space. For patients who underwent reoperation, the mean time between the initial surgery and the recurrence was 16.5 years. None of the 45 patients developed distant metastasis. It is important to preserve not only neurovascular bundles but also lower limb muscles in order to maintain ambulatory ability in the elderly patients. For well-differentiated liposarcomas of the limbs, it is important to establish a surgical margin beyond the marginal resection border and to perform muscle resection to the extent that would not greatly reduce the muscle strength. 続きを見る
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Watanabe, Koji ; Tsuchiya, Hiroyuki ; Yamamoto, Norio ; Shirai, Toshiharu ; Nishida, Hideji ; Hayashi, Katsuhiro ; Takeuchi, Akihiko ; Matsubara, Hidenori ; Nomura, Issei
出版情報: Journal of Orthopaedic Science.  18  pp.101-109,  2013-01-01.  Japanese Orthopaedic Association 日本臨床整形外科学会 / Springer Verlag
URL: http://hdl.handle.net/2297/34138
概要: Background: The aim of this study was to investigate the long-term functional capabilities of patients who underwent bon e distraction for the treatment of bone defects caused by bone tumor excision. Methods: Bone distraction was indicated for patients with stage IIB malignant bone tumors when chemotherapy was judged to be effective and an epiphysis could be preserved or for patients with low-grade or aggressive benign bone tumors. Twenty-two patients who underwent reconstruction with bone distraction and were followed up for at least 10 years were retrospectively investigated. Patients included 8 males and 14 females, with a mean age of 25.3 years. Tumor types included seven osteosarcomas, two osteofibrous dysplasias, one Ewing's sarcoma, five low-grade osteosarcomas, two adamantinomas, and five giant cell tumors. Chemotherapy was performed during bone distraction in 8 cases. Bone transport was used in 17 cases, while shortening distraction was used in 5 cases. Results: The mean distraction length was 8.1 cm, and the mean external fixation period was 301 days. The average Musculoskeletal Tumor Society score (used to measure functional outcome) was 91.5 % at mean follow-up of 202 months. Fourteen patients were able to play sports without any difficulty. Conclusions: Epiphyseal preservation and reconstruction by bone distraction require both time and effort, but can provide excellent long-term outcomes, resulting in a stable reconstruction that functionally restores the natural limb. © 2012 The Japanese Orthopaedic Association. 続きを見る