Faculty Profiles - KUNISADA Toshiyuki

Papers - KUNISADA Toshiyuki

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孤立性骨嚢腫の治療成績

中川寧子, 尾崎敏文, 国定俊之, 伊藤達男, 井上一

中部日本整形外科災害外科学会雑誌 46 ( 秋季学会 ) 46 - 46 2003.9

SYT蛋白とSSX蛋白のyeast two hybrid assayを用いた機能解析

伊藤達男, 大内田守, 尾崎敏文, 国定俊之, 森本裕樹, 大畑範英, 中川寧子, 吉田晶, 伊藤佐智夫, 清水憲二

日本癌学会総会記事 62回 536 - 536 2003.8

ある種の分子標的薬はSYT-SSX発現細胞株に特異的な抗腫瘍効果を発揮する

沼本邦彦, 伊藤達男, 尾崎敏文, 大内田守, 国定俊之, 伊藤佐智夫, 森本裕樹, 大畑範英, 中川寧子, 清水憲二, 井上一

日本整形外科学会雑誌 77 ( 8 ) S1086 - S1086 2003.8

滑膜肉腫に認められる転座遺伝子SYT-SSXのtwo hybrid assayを用いた機能解析

伊藤達男, 尾崎敏文, 大内田守, 国定俊之, 森本裕樹, 大畑範英, 中川寧子, 武田健, 沼本邦彦, 吉田晶, 伊藤佐智夫, 清水憲二, 井上一

日本整形外科学会雑誌 77 ( 6 ) S823 - S823 2003.6

Merits and weak points of diagnosis with tissue specific fusion genes

MORIMOTO Yuki

The Central Japan Journal of Orthopaedic Surgery & Traumatology 46 ( 6 ) 1067 - 1068 2003

骨軟部腫瘍におけるレセプターチロシンキナーゼ(c-kit)の発現

吉田晶, 川井章, 内藤訓子, 森本裕樹, 伊藤達男, 大畑範英, 国定俊之, 尾崎敏文, 別府保男

日本癌学会総会記事 61回 397 - 397 2002.10

Co-expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in cartilaginous tumours: a marker for malignancy? Reviewed

T Kunisada, JM Moseley, JL Slavin, TJ Martin, PFM Choong

PATHOLOGY 34 ( 2 ) 133 - 137 2002.4

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

Aim: Parathyroid hormone-related protein (PTHrP) is one of the critical factors for the differentiation and growth of chondrocytes. We examined the correlation between the co-expression of PTHrP and PTH/PTHrP receptor and the grade of malignancy in cartilaginous tumours.
Methods: We analysed PTHrP and PTH/PTHrP receptor expression in chondrosarcoma by immunohistochemistry and compared specific staining with the expression in benign cartilaginous tumours. There were 38 cartilaginous bone tumours consisting of 26 chondrosarcoma, six enchondroma and six osteochondroma. Chondrosarcoma were composed of 20 conventional chondrosarcoma (10 grade 1, seven grade 2, and three grade 3), two dedifferentiated chondrosarcoma, two clear cell chondrosarcoma, and two myxoid chondrosarcoma. We performed the standard peroxidase-labelled streptavidin-biotin detection method for immunohistochemistry using an antibody raised against PTHrP (1-14) and PTH/PTHrP receptor. The magnitude of receptor positivity of PTHrP and PTH/PTHrP in each tumour was assessed as a percentage of PTHrP and PTH/PTHrP-positive cells per thousand tumour cells in the most histologically aggressive area of the tumour.
Results: All chondrosarcoma, five of six enchondroma, and four of six osteochondroma showed PTHrP-positive cells, and all chondrosarcoma, five of six enchondroma and five of six osteochondroma showed PTHrP receptor-positive cells. The grade of malignancy correlated with the percentage of both PTHrP and PTH/PTHrP receptor-positive tumour cells (P<0.0001, either). Each grade of chondrosarcoma showed statistically higher expression of both PTHrP and PTH/PTHrP receptor than benign cartilaginous tumour.
Conclusion: This is the first report of the co-expression of PTHrP and PTH/PTHrP receptor in chondrosarcoma. PTHrP and PTH/PTHrP receptor positivity may be valuable for differentiating between benign and malignant cartilaginous tumours.

DOI： 10.1080/003130201201117936

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Endostatin inhibits adhesion of endothelial cells to collagen I via alpha(2)beta(1) integrin, a possible cause of prevention of chondrosarcoma growth Reviewed

T Furumatsu, N Yamaguchi, K Nishida, A Kawai, T Kunisada, M Namba, H Inoue, Y Ninomiya

JOURNAL OF BIOCHEMISTRY 131 ( 4 ) 619 - 626 2002.4

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE BIOCHEMICAL SOC

Endostatin derived from collagen XVIII is a potent endogenous anti-angiogenic factor that induces regression of various tumors of epithelial origin. Endostatin has been shown to inhibit endothelial cell functions, however, its effect remains controversial. We first attempted here to apply the inhibitory effect of recombinant human endostatin on chondrosarcomas, which originate from the mesenchyme, in nude mice. Endostatin induced reduction of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effect on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration on and attachment to collagen I but did not affect the proliferation of endothelial cells. Although the migration of endothelial cells was stimulated by angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence and absence of the stimulants. Moreover, the inhibitory effect against endothelial cell attachment to collagen I was attenuated or modulated in the presence of neutralizing antibodies of alpha(2), alpha(5)beta(1), and alpha(V)beta(3) integrins but not that of alpha(1) integrin. Our results suggest that endostatin might suppress the alpha(2)beta(1) integrin function of endothelial cells via alpha(5)beta(1), or alpha(V)beta(3), integrin. We propose here that endostatin might be effective for anti-angiogenic therapy for human chondrosarcomas through the suppression of alpha(2)beta(1) integrin functions in endothelial cells.

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Wound complications following pre-operative radiotherapy for soft tissue sarcoma Reviewed

T Kunisada, SY Ngan, G Powell, PFM Choong

EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 28 ( 1 ) 75 - 79 2002.2

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO LTD

Aims: We analysed wound complications in 43 patients with soft tissue sarcoma who were treated with combined pre-operative radiotherapy and surgery
Methods: All patients received the same protocol of pre-operative radiotherapy at our institution.
Results: Thirty-six (84%) patients developed acute skin toxicity following radiotherapy. After wide local excision, 15 patients required primary soft tissue reconstruction with vascularized muscle transfer and four patients underwent free skin flap to enable wound closure as part of their primary surgery. Nineteen patients (44%) developed postoperative wound complications including 10 (23%) patients who required an additional surgical procedure. Four (27%) patients developed flap necrosis in a group of 15 who underwent primary vascularized soft tissue transfer. All required a second vascularized muscular flap. One elderly patient, who had grade 3 acute radiation skin toxicity, had an arterial graft and total hip arthroplasty for a femoral artery aneurysm and an avascular necrosis of the hip, respectively. In our series, age ( 40 years) was the only impact factor influencing wound complication after surgery following radiotherapy (P=0.06).
Conclusions: Site of tumour, radiation field size, surgical resection volume, grade of acute radiation toxicity, comorbidity, and smoking were not demonstrated to have predictive value in wound complication following preoperative radiotherapy. Although previous papers suggested that vascularized soft tissue transfer could be useful reducing wound morbidity, our results could not confirm this. (C) 2002 Harcourt Publishers Ltd.

DOI： 10.1053/ejso.2001.1213

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Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-gamma.

Nishida K, Furumatsu T, Takada I, Kawai A, Yoshida A, Kunisada T, Inoue H

Br J Cancer 2002

Reconstruction of the proximal humerus with the clavicle after tumor resection: a case report.

Ozaki T, Hashizume H, Kunisada T, Kawai A, Nishida K, Sugihara S, Inoue H

Clin Orthop 2001

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA classⅠallele

Hiraki A, Ikeda K, Yoshino T, Kaneshige T, Kiura K, Kunisada T, Fujiwara K, Tanimoto M, Harada M

Biochem Biophys Res Comm 2001

Major reconstruction for periacetabular metastasis - Early complications and outcome following surgical treatment in 40 hips Reviewed

T Kunisada, PFM Choong

ACTA ORTHOPAEDICA SCANDINAVICA 71 ( 6 ) 585 - 590 2000.12

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS AS

We performed 40 total hip arthroplasties with pelvic reconstruction in 37 patients with metastatic periacetabular tumor. 3 patients underwent bilateral periacetabular reconstructive surgery and 2 of these had bilateral procedures at the single operation. There were 8 Harrington class I, 7 class II, and 25 class III lesions, A modified Harrington procedure was employed. All patients showed improvements in hip pain, analgesic use, ambulation and mobility postoperatively, 1 prosthetic dislocation occurred after a fall at home 2 months fallowing surgery. 2 patients had pulmonary emboli during the femoral procedure, 1 of whom died during surgery. There mere no prosthetic loosenings. Preoperative CT and/or MRI are important for the study of metastatic involvement of acetabular bone, Durability of reconstruction requires appropriate use of acetabular mesh, Steinmann pins, acetabular reinforcement rings and long-stem femoral prostheses. Careful patient selection may improve quality of life. A sequential bilateral procedure should be considered for some patients.

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Synovial sarcoma with a large hematoma in the inguinal region Reviewed

N Naito, T Ozaki, T Kunisada, A Kawai, T Dan'ura, Y Morimoto, H Inoue

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY 120 ( 9 ) 533 - 534 2000.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER-VERLAG

We report the case of a patient with synovial sarcoma and a large hematoma of the inguinal region. The patient underwent tumor resection of the lower 2/3 of the acetabulum after preoperative chemotherapy. Twenty-four months after surgery, she is alive without any relapse and can walk without support.

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Giant schwannoma of the back Reviewed

Eiichi Takada, Toshifumi Ozaki, Toshiyuki Kunisada, Yoshiaki Harada, Hajime Inoue

Archives of Orthopaedic and Trauma Surgery 120 ( 7-8 ) 467 - 469 2000

Electrophoretic and serologic characterization of 56 kDa antigen (M56) with autologous serum derived from a chondrosarcoma patient: A shared antigen of immunoresponses in cancer and autoimmune diseases Reviewed

K Fujiwara, H Udono, T Kunisada, A Kawai, H Inoue, M Takigawa, M Namba, E Nakayama

ELECTROPHORESIS 20 ( 17 ) 3335 - 3342 1999.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-V C H VERLAG GMBH

We investigated whether antibodies specific to autologous cancer cells are produced in the peripheral blood of patients with chondrosarcoma. There have been few reports on the investigation of the immune responses, such as autologous antibody production, to chondrosarcoma. Here, tumor-associated antigens were separated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and detected by immunoenzymatic amplification. A 56 kDa molecule (M56) was detected in the serum from patients' peripheral blood. M56 is ubiquitously expressed in various kinds of tissue-derived cells. However, the molecule seemed to be retained mostly in the cytosolic compartment of lymphoid cells, while it was expressed on the cell surface of nonlymphoid cancer cells. Furthermore, the antibodies reactive to the 56 kDa molecule were frequently observed in sera derived from patients with other cancers and autoimmune diseases as compared to the sera from healthy control donors, suggesting that M56 is a common target molecule of immune responses in patients with various cancers and autoimmune diseases.

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Insertion of the patella tendon after prosthetic replacement of the proximal tibia Reviewed

T Ozaki, T Kunisada, A Kawai, Y Takahara, H Inoue

ACTA ORTHOPAEDICA SCANDINAVICA 70 ( 5 ) 527 - 529 1999.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SCANDINAVIAN UNIVERSITY PRESS

We describe the technique and the results of a method to reconstruct the patellar tendon insertion to a tumor prosthesis by wrapping an artificial mesh around the prosthesis, followed by suturing the patellar tendon and a gastrocnemius flap to the mesh.

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Imaging assessment of the responses of osteosarcoma patients to preoperative chemotherapy - Angiography compared with thallium-201 scintigraphy Reviewed

T Kunisada, T Ozaki, A Kawai, S Sugihara, K Taguchi, H Inoue

CANCER 86 ( 6 ) 949 - 956 1999.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

BACKGROUND. Assessment of the responses of osteosarcoma patients to preoperative chemotherapy is of clinical importance. The purpose of this study was to estimate the accuracy of angiography and thallium-201 scintigraphy, compared with histology, in assessing the responses of patients with osteosarcoma to preoperative chemotherapy.
METHODS, Nineteen patients with osteosarcoma who were diagnosed between 1992 and 1997 were studied. The findings of angiography and thallium-201 scintigraphy before and after preoperative chemotherapy were compared with the percentage of necrosis of tumor cells and the response grade as determined histologically. Quantitative analysis of the isotopic uptake by thallium-201 scintigraphy before and after chemotherapy, defined as the alteration ratio, was correlated with the percentage of tumor necrosis.
RESULTS, Angiography yielded a sensitivity of 88%, a specificity of 73%, and a predictive accuracy of positive test of 70%, whereas thallium-201 scintigraphy achieved 88%, 100%, and 100%, respectively. Both angiographic and scintigraphic assessment showed a significant correlation with response grade as determined histologically (P < 0.05 and P < 0.0003, respectively). The alteration ratio of thallium-201 scintigraphy showed a strong, highly significant correlation with the percentage of tumor necrosis (P < 0.0001).
CONCLUSIONS. A change in the tumor uptake of thallium-201 scintigraphy after preoperative chemotherapy can predict the tumor necrosis in osteosarcoma precisely. Thallium scintigraphy is a noninvasive technique and seems to be more useful than angiography in assessing the response of osteosarcoma to preoperative chemotherapy. (C) 1999 American Cancer Society.

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Reconstruction of the hip abductors after resection of the proximal femur Reviewed

T Ozaki, S Kaneko, T Kunisada, A Kawai, T Dan'ura, N Naito, H Inoue

INTERNATIONAL ORTHOPAEDICS 23 ( 3 ) 182 - 183 1999.8

Angiography for assessment of preoperative chemotherapy in musculoskeletal sarcomas Reviewed

J Fujii, T Ozaki, A Kawai, T Kunisada, S Sugihara, H Inoue

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH ( 360 ) 197 - 206 1999.3

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Eleven abnormal findings of digital subtraction angiography were analyzed in 25 patients with bone sarcoma and in 23 patients with soft tissue sarcoma. The relation between digital subtraction angiographic findings and the histologic effect of chemotherapy was evaluated. Digital subtraction angiography was performed with the patient under local anesthesia with the Seldinger technique, using an ADVANT X unit. Contrast medium was injected at a rate of 4 to 6 mi per second, with the usual single bolus dose of approximately 6 to 8 mi. Eleven abnormal findings included tumor stain, hypervascularity, arterial distortion, vascular stretch, arterial dilatation, arteriovenous shunt, arterial encasement, occlusion, blood pool, caliber with irregular wall, and dilatation of draining vein. Each finding after preoperative chemotherapy was compared with that before chemotherapy and divided into three grades; Grade I, not effective; Grade 2, effective; and Grade 3, very effective. Angiographic Grades 2 and 3 were defined as responders. The histologic effect was examined and scored according to the modified classification proposed by Huvos. Histologic Grades 1 and 2 were classified as nonresponders and Grades 3 and 4 as good responders. In bone sarcomas, hypervascularity and tumor stain were seen in all patients. In soft tissue sarcomas, tumor stain was shown in all 23 patients and hypervascularity was seen in 21 patients. Tumor stain, hypervascularity, vascular stretch, and arterial encasement were correlated closely with histologic findings and showed an accuracy equal to or greater than 70%. When these four findings changed to angiographic Grade 3 after preoperative chemotherapy, 90% of patients had good histologic outcome.

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