Faculty Profiles - KUNISADA Toshiyuki

治療後14年で肺転移をきたしたEwing肉腫の1例

米田泰史, 国定俊之, 田端雅弘, 二宮崇, 森本裕樹, 尾崎敏文

中部日本整形外科災害外科学会雑誌 52 ( 春季学会 ) 205 - 205 2009.3

Aneurysmal bone cyst of the calcaneus

MIYAKE Yoshiaki

The Central Japan Journal of Orthopaedic Surgery & Traumatology 52 ( 4 ) 971 - 972 2009

Refraction-based 2D, 2.5D and 3D medical imaging: Stepping forward to a clinical trial Reviewed

Masami Ando, Hiroko Bando, Tokiko Endo, Shu Ichihara, Eiko Hashirnoto, Kazuyuki Hyodo, Toshiyuki Kunisada, Gang Li, Anton Maksimenko, Kensaku Mori, Daisuke Shimao, Hiroshi Sugiyama, Tetsuya Yuasa, Ei Ueno

EUROPEAN JOURNAL OF RADIOLOGY 68 ( 3 ) S32 - S36 2008.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

An attempt at refraction-based 2D, 2.5D and 3D X-ray imaging of articular cartilage and breast carcinoma is reported. We are developing very high contrast X-ray 2D imaging with XDFI (X-ray dark-field imaging), X-ray CT whose data are acquired by DEI (diffraction-enhanced imaging) and tomosynthesis due to refraction contrast. 2D and 2.5D images were taken with nuclear plates or with X-ray films. Microcalcification of breast cancer and articular cartilage are clearly visible. 3D data were taken with an X-ray sensitive CCD camera. The 3D image was successfully reconstructed by the use of an algorithm newly made by our group. This shows a distinctive internal structure of a ductus lactiferi (milk duct) that contains inner wall, intraductal carcinoma and multifocal calcification in the necrotic core of the continuous DCIS (ductal carcinoma in situ). Furthermore consideration of clinical applications of these contrasts made LIS to try tomosynthesis. This attempt was satisfactory from the view point of articular cartilage image quality and the skin radiation close. (C) 2008 Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.ejrad.2008.04.033

Shift-and-add tomosynthesis of a finger joint by X-ray dark-field imaging: Difference due to tomographic angle Reviewed

Daisuke Shimao, Toshiyuki Kunisada, Hiroshi Sugiyama, Masami Ando

EUROPEAN JOURNAL OF RADIOLOGY 68 ( 3 ) S27 - S31 2008.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

A tomogram of a finger joint showing articular cartilage was generated based on X-ray dark-field imaging (XDFI) using the shift-and-add tomosynthesis algorithm. The experiment was performed at beamline 14B of the Photon Factory in Tsukuba, Japan, using synchrotron X-rays from a vertical wiggler. The incident X-ray energy was 36.0keV. The X-ray optics for XDFI comprised two Si crystals: an asymmetric Cut Si (2 2 0) monochromator-collimator and a 1.1-mm thick Si (2 2 0) Laue-case analyzer. The object was an intact cadaveric proximal interphalangeal joint fixed in formalin. Raw projection data were acquired by XDFI in a total of 41 views through an angle of 20 degrees in 0.5 degrees increments. The object and detector were synchronously rotated such that the fulcrum plane in the object and detector plane remained parallel. The X-ray dose for one piece of raw projection data was set to one-eleventh of that for one standard projection image by XDFI. Eleven views through an angle of 10 degrees in increments of 1 degrees of all 41 appropriately shifted raw projection data were added to produce arbitrary tomograms parallel to the fulcrum plane. We obtained a clear tomogram of the finger joint including the articular cartilage with the moderate artifact Peculiar to tomosynthesis. Consequently, arbitrary tomograms can be obtained for the same X-ray dose as that received for one standard projection image by XDFI. The fact that an inner structure such as articular cartilage, which is invisible to conventional X-ray imaging methods, has been Visualized on a tomogram with preserved refraction-enhanced contrast, is of considerable significance to clinical medicine. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ejrad.2008.04.037

X-ray dark field imaging of human articular cartilage: Possible clinical application to orthopedic surgery Reviewed

Toshiyuki Kunisada, Daisuke Shimao, Hiroshi Sugiyama, Ken Takeda, Toshifumi Ozaki, Masami Ando

EUROPEAN JOURNAL OF RADIOLOGY 68 ( 3 ) S18 - S21 2008.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Despite its convenience and non-invasiveness on daily clinical use, standard X-ray radiography cannot show articular cartilage. We developed a novel type of X-ray dark field imaging (DFI), which forms images only by a refracted beam with very low background illumination. We examined a disarticulated distal femur and a shoulder joint with surrounding soft tissue and skin, both excised from a human cadaver at the BL20B2 synchrotron beamline at SPring-8. The field was 90 mm wide and 90 mm high. Articular cartilage of the disarticulated distal femur was obvious on DFI, but not on standard X-ray images. Furthermore, DFI allowed visualization in situ of articular cartilage of the shoulder while covered with soft tissue and skin. The gross appearance of the articular cartilage on the dissected section of the proximal humerus was identical to the cartilage shown on the DFI image. These results suggested that DFI could provide a clinically accurate method of assessing articular cartilage. Hence, DFI would be a useful imaging tool for diagnosing joint disease such as osteoarthritis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ejrad.2008.04.034

ヒストン脱アセチル化酵素阻害剤とDNA脱メチル化剤の併用による滑膜肉腫細胞株に対する抗腫瘍効果の検討

佐藤千明, 吉田晶, 森本裕樹, 米田泰史, 佐々木剛, 国定俊之, 大内田守, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S1228 - S1228 2008.8

骨肉腫患者における葉酸代謝関連遺伝子の一塩基多型の検討

森本裕樹, 吉田晶, 大内田守, 米田泰史, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S926 - S926 2008.8

滑膜肉腫関連蛋白の細胞内局在に影響を与える薬剤および蛋白に関する検討

米田泰史, 大内田守, 神崎浩孝, 吉田晶, 佐々木剛, 森本裕樹, 国定俊之, 清水憲二, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S1023 - S1023 2008.8

Photodynamic therapy with ATX-S10 center dot Na(II) inhibits synovial sarcoma cell growth Reviewed

Ken Takeda, Toshiyuki Kunisada, Shinichi Miyazawa, Yoshinori Nakae, Toshifumi Ozaki

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 466 ( 7 ) 1726 - 1733 2008.7

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

Photodynamic therapy (PDT) is an effective cancer treatment modality that allows selective destruction of malignant tumor cells. We asked whether PDT could inhibit in vivo and in vitro growth of synovial sarcoma cells. We analyzed PDT using ATX-S10 center dot Na(II) and a diode laser for a synovial sarcoma cell line (SYO-1). Photodynamic therapy with ATX-S10 center dot Na(II) showed an in vitro cytotoxic effect on the cultured SYO-1 cells. The in vitro effect of PDT depended on the treatment concentration of ATX-S10 center dot Na(II) and the laser dose of irradiation. ATX-S10 center dot Na(II) was detected in the tumor tissue specimens that were excised from nude mice bearing SYO-1 within 6 hours after intravenous injection, but it was eliminated from the tumor 12 hours after injection. Photodynamic therapy suppressed the tumor growth of nude mice bearing SYO-1, and high-dose irradiation induced no viable tumor cells in histologic specimens. Photodynamic therapy performed after marginal resection of the tumor of nude mice bearing SYO-1 reduced the rate of local recurrence of the tumor. Our results suggest PDT using ATX-S10 center dot Na(II) and laser irradiation may be a potentially useful treatment for synovial sarcoma, especially to reduce the surgical margin and preserve critical anatomic structures adjacent to the tumor.

DOI： 10.1007/s11999-008-0284-6

橋本病を合併したMazabraud syndromeの1例

Single nucleotide polymorphism in reuced folate carrier-1 gene and methyleneterathydrofolate reductase gene in patients with osteosarcoma

Y. Morimoto, A. Yoshida, M. Ouchida, T. Kunisada, K. Shimizu, T. Ozaki

EJC SUPPLEMENTS 6 ( 9 ) 117 - 118 2008.7

大畑範英, 森本裕樹, 吉田晶, 佐々木剛, 米田泰史, 国定俊之, 大内田守, 尾崎敏文

日本整形外科学会雑誌 82 ( 6 ) S853 - S853 2008.6

Chondrosarcoma and PeroxisomeProliferator-Activated Receptor.

Nishida K, Kunisada T, Shen ZN, Kadota Y, Hashizume K, Ozaki T

PPAR Research 2008 1 - 7 2008

New approach for assessing vascular distribution within bone tumors using dynamic contrast-enhanced MRI Reviewed

Yukio Kawakami, Toshiyuki Kunisada, Shinsuke Sugihara, Atsushi Ono, Keiichiro Nishida, Nobuhiro Abe, Akira Kawai, Kazuo Fujiwara, Yuki Morimoto, Toshifumi Ozaki

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 133 ( 10 ) 697 - 703 2007.10

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

Purpose To differentiate benign from malignant bone tumors by analyzing the vascular distribution within bone tumors with dynamic contrast-enhanced MRI.
Methods We studied dynamic contrast-enhanced MRI for 49 bone tumors (22 malignant and 27 benign tumors). Seven small regions of interest (ROI) were set inside the largest portion of each tumor. Four ROI were placed evenly on the periphery and three ROI were placed evenly on the line of the longest breadth within the tumor. The slope of the curve (%Slope) was calculated on the time-intensity curves of the whole tumor and of each ROI. The variance values for the %Slope of the ROI were calculated to assess the dispersion of the intensity change at each ROI within the tumor.
Results Mean value of the %Slopes of whole tumor regions for malignant bone tumors (70.4 +/- 60.3%) was significantly higher than that for benign bone tumors (37.6 +/- 52.9%) (P = 0.015), although giant cell tumor (GCT), a locally aggressive tumor, had a relatively higher %Slope. Mean value of the variance of %Slopes for malignant bone tumors (3485.9 +/- 5942.5) was significantly higher than that for all benign tumors (470.4 +/- 583.9) (P = 0.012), indicating that the %Slope values of seven ROI within malignant bone tumors varied more widely compared with the ROI inside benign bone tumors. GCT also demonstrated a lower value.
Conclusion Our method of analyzing the signal intensity change at seven separate regions that evaluates the vascular distribution within a tumor could be a useful tool for differentiating between benign and malignant bone tumors.

DOI： 10.1007/s00432-006-0190-9

滑膜肉腫特異的転座型融合蛋白SS18-SSXおよびSS18、SSX蛋白の細胞内局在の解析

骨肉腫における6q16-23の高頻度染色体欠失の研究(High frequent allelic loss of chromosome 6q16-23 in osteosarcoma: Involvement of cyclin C in osteosarcoma)

大畑範英, 吉田晶, 伊藤佐智夫, 国定俊之, 森本裕樹, 神崎浩孝, 尾崎敏文, 清水憲二, 大内田守

日本癌学会総会記事 66回 345 - 345 2007.8

米田泰史, 大内田守, 神崎浩孝, 国定俊之, 清水憲二, 尾崎敏文

日本整形外科学会雑誌 81 ( 8 ) S1119 - S1119 2007.8

Refraction-enhanced tomosynthesis of a finger joint by X-ray dark-field imaging Reviewed

Daisuke Shimao, Toshiyuki Kunisada, Hiroshi Sugiyama, Masami Ando

JAPANESE JOURNAL OF APPLIED PHYSICS PART 2-LETTERS & EXPRESS LETTERS 46 ( 25-28 ) L608 - L610 2007.7

Language：English Publishing type：Research paper (scientific journal) Publisher：INST PURE APPLIED PHYSICS

A finger joint tomogram based on X-ray dark-field imaging (XDFI) was demonstrated using the simplest shift-and-add tomosynthesis algorithm. Raw XDFI image data for tomosynthesis were acquired in a total of 11 views through 10 degrees, in increments of 1 degrees, by rotating the object and detector synchronously. Incident X-ray energy was monochromatic 36.0keV, derived from synchrotron radiation. The total dosage in acquiring 11 views for raw image data was equivalent to that of one XDFI image. A clear tomogram was obtained of a finger joint (including articular cartilage, which is invisible by conventional tomosynthesis) without an increase in X-ray dosage.

DOI： 10.1143/JJAP.46.L608

On detailed contrast of biomedical object in X-ray dark-field imaging Reviewed

Daisuke Shimao, Hiroshi Sugiyama, Toshiyuki Kunisada, Kazuyuki Hyodo, Koichi Mori, Masami Ando

SYNCHROTRON RADIATION INSTRUMENTATION, PTS 1 AND 2 879 1960 - + 2007

Language：English Publishing type：Research paper (international conference proceedings) Publisher：AMER INST PHYSICS

Over the past 10 years, refraction-based X-ray imaging has been studied together with a perspective view to clinical application. X-ray Dark-Field Imaging that utilizes a Laue geometry analyzer has recently been proposed and has the proven ability to depict articular cartilage in an intact human finger. In the current study, we researched detailed image contrast using X-ray Dark-Field Imaging by observing the edge contrast of an acrylic rod as a simple case, and found differences in image contrast between the right and left edges of the rod. This effect could cause undesirable contrast in the thin articular cartilage on the head of the phalanx. To avoid overlapping with this contrast at the articular cartilage, which would lead to a wrong diagnosis, we suggest that a joint surface on which articular cartilage is located should be aligned in the same sense as the scattering vector of the Lane case analyzer crystal. Defects of articular cartilage were successfully detected under this condition. When utilized under appropriate imaging conditions, X-ray Dark-Field Imaging will be a powerful tool for the diagnosis of arthropathy, as minute changes in articular cartilage may be early-stage features of this disease.

DOI： 10.1063/1.2436458

Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: Involvement of cyclin C in osteosarcoma Reviewed

Norihide Ohata, Sachio Ito, Aki Yoshida, Toshiyuki Kunisada, Kunihiko Numoto, Yoshimi Jitsumori, Hirotaka Kanzaki, Toshifumi Ozaki, Kenji Shimizu, Mamoru Ouchida

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18 ( 6 ) 1153 - 1158 2006.12

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q, 8p, 10p and 10q. To define the narrow rearranged region on chromosome 6 with higher resolution, loss of heterozygosity (LOH) analysis was performed with 21 microsatellite markers. Out of 31 cases, 23 cases (74%) showed allelic loss at least with one marker on chromosome 6q. We identified two distinct commonly deleted regions on chromosome 6 using markers D6S1565 located at 6q16 and 6q23MS1 at 6q23. The expression analysis of genes located at the deleted region was performed, and the decreased mRNA expression of the CCNC gene, one of the regulators of cell cycle, was detected. Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection. Fine mapping of the deleted region containing a possible tumor suppressor gene and the transfection assay suggest that the CCNC is a candidate tumor suppressor gene.