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写真a

コイズミ トシユキ
小泉 敏之
Toshiyuki Koizumi
所属
医学研究科 医科学専攻 口腔外科学 講師
医学部 医学科
職名
講師
ホームページ
プロフィール
平成6年 3月 北海道大学歯学部 歯学科 卒業
平成12年 3月 東京大学大学院医学系研究科 外科学専攻(博士課程) 修了
外部リンク

学位

  • 医学博士 ( 東京大学 )

研究キーワード

  • bone destruction

  • 口腔がん

  • IL-6

  • 血管柄付神経移植

  • 早期軸索再生

  • aPKCλ/ι

  • Cancer stem cell

  • gene targeting

  • 口腔扁平上皮癌

  • 遊離神経移植

  • antisense

  • gene therapy

  • iNOS

研究分野

  • ライフサイエンス / 外科系歯学

経歴

  • 横浜市立大学   医学部   講師

    2014年

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  • 横浜市立大学 附属病院

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論文

  • Prognostic value of 2-[(18) F]fluoro-2-deoxy-D-glucose positron emission tomography for patients with oral squamous cell carcinoma treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy 査読

    Mai Shimizu, Kenji Mitsudo, Izumi Koike, Masataka Taguri, Toshinori Iwai, Toshiyuki Koizumi, Senri Oguri, Mitomu Kioi, Makoto Hirota, Tomio Inoue, Iwai Tohnai

    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY   121 ( 3 )   239 - 247   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Objective. To investigate whether 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) uptake of primary tumor in oral squamous cell carcinoma (OSCC) could predict prognosis.
    Study Design. Sixty-nine patients with OSCC who underwent retrograde superselective intra-arterial chemoradiotherapy were recruited and underwent dual-time-point FDG positron emission tomography twice, before treatment and 4 weeks after treatment. FDG uptake was defined as the standardized uptake value (SUVmax). The retention index (RI) and the percent change in SUV (% change SUV), derived from the dual-time-point scan, were calculated.
    Results. On univariate analysis, patients with high pre-SUV, RI, and percent change SUV values had significantly worse overall survival and disease-free survival compared with patients with low values. On multivariate analysis, high pre-RI (>= 20.6%) and high percent change SUV (>= 60.0%) (delayed-image) were associated with significantly worse overall survival. High pre-SUV (>= 9.6) (delayed-image) and high pre-RI (>= 20.6%) were associated with significantly shorter disease-free survival.
    Conclusions. Dual-time-point FDG positron emission tomography in OSCC provided prognostic information and predicted patient outcome.

    DOI: 10.1016/j.oooo.2015.10.018

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  • A simple evaluation method for early detection of bisphosphonate-related osteonecrosis of the mandible using computed tomography 査読

    Hayato Hamada, Akira Matsuo, Toshiyuki Koizumi, Takafumi Satomi, Daichi Chikazu

    JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY   42 ( 6 )   924 - 929   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHURCHILL LIVINGSTONE  

    Objectives: The aim of this study was to establish a simple method for the early detection of bisphosphonate-related osteonecrosis of the jaw (BRONJ) using computed tomography (Cr).
    Materials and methods: CT images of the mandible were obtained from a total of 20 patients with BRONJ and 20 control subjects. BRONJ was classified into 2 groups, with bone exposure (Stage 1-3 BRONJ) or without (Stage 0 BRONJ). In each patient, 15 transaxial Cr images were selected and 30 configured regions of interest (ROI) were identified. The ANOVA test was applied to test the relationship between the severity of systemic risk factors.
    Results: Regarding the local status of the mandible, significant differences were observed among the Stage 0 BRONJ, Stage 1-3 BRONJ, non-BRONJ and control groups in the cancellous bone CT radiodensity values, but there were no significant differences between the Stage 0 and Stage 1-3 BRONJ groups. In the cortical bone widths, significant differences were observed only between BRONJ and the controls.
    Conclusions: Measuring cancellous bone CT radiodensity value has the potential to be a simple and quantitative method to detect the early stages of BRONJ. (c) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jcms.2014.01.012

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  • Solitary myofibroma of the mandible: an immunohistochemical and ultrastructural study with a review of the literature 査読

    Takafumi Satomi, Michihide Kohno, Ai Enomoto, Harutsugu Abukawa, Ko Fujikawa, Toshiyuki Koizumi, Daichi Chikazu, Jun Matsubayashi, Toshitaka Nagao

    MEDICAL MOLECULAR MORPHOLOGY   47 ( 3 )   176 - 183   2014年9月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    A solitary myofibroma (MF) is an unusual spindle cell neoplasm that usually arises in the soft tissue, skin, or bone of the head and neck region in infancy. We report an extremely rare case of MF of the mandible in an 18-year-old Japanese woman together with the conventional histologic, immunohistochemical, and electron microscopic findings. The tumor was well circumscribed and composed of fibroblast-like or myofibroblast-like spindle cells. On immunohistochemical evaluation the tumor cells were positive for vimentin, alpha-smooth muscle actin, HHF-35, and calponin, but negative for neurogenic antigens and markers for vascular endothelial cells. The Ki-67 labeling index was 10 % and the p53 labeling index was 10 %. Ultrastructural examination revealed smooth muscle cell differentiation. The patient was treated by surgical resection and underwent follow-up without any signs of recurrence. MF presents a wide range of differential diagnosis, including benign and malignant neoplasms. Therefore, accurate diagnosis may avoid an unnecessarily aggressive therapy.

    DOI: 10.1007/s00795-013-0062-8

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  • Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases 査読

    Kenji Mitsudo, Toshiyuki Koizumi, Masaki Iida, Toshinori Iwai, Hideyuki Nakashima, Senri Oguri, Mitomu Kioi, Makoto Hirota, Izumi Koike, Masaharu Hata, Iwai Tohnai

    RADIOTHERAPY AND ONCOLOGY   111 ( 2 )   306 - 310   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Purpose: To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy.
    Materials and methods: One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60 mg/m(2), cisplatin, total 150 mg/m(2)) and daily concurrent radiotherapy (total of 60 Gy) for 6 weeks.
    Results: The median follow-up for all patients was 46.2 months (range, 10-76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients.
    Conclusion: Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.radonc.2014.03.005

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  • Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy for gingival carcinoma 査読

    Y. Mukai, M. Hata, K. Mitsudo, I. Koike, T. Koizumi, S. Oguri, M. Kioi, M. Omura, I. Tohnai, T. Inoue

    STRAHLENTHERAPIE UND ONKOLOGIE   190 ( 2 )   181 - 185   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:URBAN & VOGEL  

    Purpose. The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma.
    Methods and materials. In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors.
    Results. Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment.
    Conclusion. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma.

    DOI: 10.1007/s00066-013-0468-1

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  • Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases 査読

    Kenji Mitsudo, Toshiyuki Koizumi, Masaki Iida, Toshinori Iwai, Senri Oguri, Noriyuki Yamamoto, Yoshiyuki Itoh, Mitomu Kioi, Makoto Hirota, Iwai Tohnai

    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS   83 ( 5 )   E639 - E645   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer.
    Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m(2); CDDP, total 100-150 mg/m(2)) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks.
    Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971; 1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively.
    Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3 metastatic lymph nodes experienced a high rate of distant metastases. (C) 2012 Elsevier Inc.

    DOI: 10.1016/j.ijrobp.2012.02.057

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  • Cyclooxygenase-2 activity is essential for the osseointegration of dental implants 査読

    D. Chikazu, K. Tomizuka, T. Ogasawara, H. Saijo, T. Koizumi, Y. Mori, Y. Yonehara, T. Susami, T. Takato

    INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY   36 ( 5 )   441 - 446   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CHURCHILL LIVINGSTONE  

    The aim of this study was to examine the effect of cyclooxygenase (COX)-2 on bone response after the placement of implants in the femurs of mice. titanium implants 1.0 mm in diameter were placed into the middle of the femurs of 9-week-old male COX-2 wild-type (COX-2(+/+)) and knockout (COX-2(-/-)) mice. For RNA analysis, the mice were killed 0, 1, 2, 4, 7 and 56 days after implantation. RNA was extracted from the bone surrounding the implants. For histological analysis, the mice were killed 4 and 8 weeks after treatment, and undecalcified sections were prepared. Contact microradiography was performed, and the sections were stained with 1% toluidine blue for histological examination. Histomorphometric measurements were obtained with a computer-based image analyser to quantify bone newly formed around the implant and the rate of implant-bone contact. Expression of COX-2 and osteocalcin mRNA was induced in bone surrounding implants in COX-2(+/+) mice, but not in COX-2(-/-) mice. In cortical bone, the implant surface was in direct contact with newly formed bone lamellae in COX-2(+/+) mice; new bone formation was minimal in COX-2(-/-) mice. These results suggest that COX-2 plays an essential role in osseointegration and provide evidence that COX-2-selective non-steroidal anti-inflammatory drugs may interfere with osseointegration clinically.

    DOI: 10.1016/j.ijom.2006.11.011

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  • Cell density and growth-dependent down-regulation of both intracellular calcium responses to agonist stimuli and expression of smooth-surfaced endoplasmic reticulum in MC3T3-E1 osteoblast-like cells 査読

    T Koizumi, H Hikiji, WS Shin, T Takato, S Fukuda, T Abe, N Koshikiya, K Iwasawa, T Toyo-oka

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 8 )   6433 - 6439   2003年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    A two-dimensional intracellular Ca2+ ([Ca2+](i)) imaging system was used to examine the relationship between [Ca2+](i) handling and the proliferation of MC3T3-E1 osteoblast-like cells. The resting [Ca2+](i) level in densely cultured cells was 1.5 times higher than the [Ca2+](i) level in sparsely cultured cells or in other cell types (mouse fibroblasts, rat vascular smooth muscle cells, and bovine endothelial cells). A high resting [Ca2+](i) level may be specific for MC3T3-E1 cells. MC3T3-E1 cells were stimulated with ATP (10 mum), caffeine (10 mm), thapsigargin (1 mum), or ionomycin (10 mum), and the effect on the [Ca2+](i) level of MC3T3-E1 cells was studied. The percentage of responding cells and the degree of [Ca2+](i) elevation were high in the sparsely cultured cells and low in densely cultured cells. The rank order for the percentage of responding cells and magnitude of the Ca2+ response to the stimuli was ionomycin > thapsigargin = ATP > caffeine and suggests the existence of differences among the various [Ca2+](i) channels. All Ca2+ responses in the sparsely cultured MC3T3-E1 cells, unlike in other cell types, disappeared after the cells reached confluence. Heptanol treatment of densely cultured cells restored the Ca2+ response, suggesting that cell-cell contact is involved with the confluence-dependent disappearance of the Ca2+ response. Immunohistological analysis of type 1 inositol trisphosphate receptors and electron microscopy showed distinct expression of inositol trisphosphate receptor proteins and smooth-surfaced endoplasmic reticulum in sparsely cultured cells but reduced levels in densely cultured cells. These results indicate that the underlying basis of confluence-dependent [Ca2+](i) regulation is down-regulation of smooth-surfaced endoplasmic reticulum by cell-cell contacts.

    DOI: 10.1074/jbc.M210243200

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  • Peroxynitrite production by TNF-alpha and IL-1beta: implication for suppression of osteoblastic differentiation. 査読

    Am J Physiol Endocrinol Metab.   278 ( 6 )   E1031 - E1037   2000年6月

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    記述言語:英語  

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  • Strain- and age-dependent loss of sarcoglycan complex in cardiomyopathic hamster hearts and its re-expression by delta-sarcoglycan gene transfer in vivo 査読

    T Kawada, Y Nakatsuru, A Sakamoto, T Koizumi, WS Shin, Y Okai-Matsuo, J Suzuki, Y Uehara, M Nakazawa, H Sato, T Ishikawa, T Toyo-oka

    FEBS LETTERS   458 ( 3 )   405 - 408   1999年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The delta-sarcoglycan (SG) gene is deleted in hamsters with hereditary cardiomyopathies, Immunological analyses of heart before, but not after, the progression of cardiomyopathy (CM) revealed that the BIO 14.5 strain, a model of hypertrophic CM, heterogeneously preserved alpha- and II-SG with loss of beta- and delta-SG, In contrast, the TO-2 strain, a model of dilated CM, did not show,v either SG, Furthermore, in vivo transfer of the full length delta-SG gene to TO-2 hearts expressed all four SGs, Thus, this age- and strain-dependent features suggest a more feasible setting for TO-2 than BIO 14.6 to verify both CM progression and the efficacy of gene therapy, (C) 1999 Federation of European Biochemical Societies.

    DOI: 10.1016/S0014-5793(99)01164-3

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  • Precise identification of gene products in hearts after in vivo gene transfection, using sendai virus-coated proteoliposomes 査読

    T Kawada, WS Shin, Y Nakatsuru, T Koizumi, A Sakamoto, T Nakajima, Y Okai-Matsuo, M Nakazawa, H Sato, T Ishikawa, T Toyo-Oka

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   259 ( 2 )   408 - 413   1999年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC  

    Both efficient gene transfer and the exact identification of gene product are required for gene therapy. Gene transfection of green fluorescence protein (GFP) might be useful for the reporter. After in vivo cotransfection of GFP and beta-galactosidase (beta-Gal) genes in Sendai virus-coated proteoliposomes to rat hearts, we compared the sensitivity and specificity of three methods: GFP detection, histochemical staining (HC) of beta-Gal activity, and immunostaining (LS) of the beta-Gal protein. Fluorescence microscopy and double staining of HC and IS revealed that both GFP and IS were equally sensitive and fourfold superior to HC at the peak of gene expression. However, different from skeletal muscle, the GFP of transfected cardiomyocytes showed two demerits: the fluorescence quenching due to the intense staining of beta-Gal activity, and nonspecific autofluorescence from myocardium. Thus, specific IS would be so far the most reliable to identify the gene product in heart. (C) 1999 Academic Press.

    DOI: 10.1006/bbrc.1999.0764

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  • Direct action of nitric oxide on osteoblastic differentiation 査読

    H Hikiji, WS Shin, S Oida, T Takato, T Koizumi, T Toyooka

    FEBS LETTERS   410 ( 2-3 )   238 - 242   1997年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The effect of nitric oxide (NO) on osteoblastic differentiation was examined in cultured mouse osteoblasts. Interleukin-1 beta and tumor necrosis factor-alpha expressed inducible NO synthase gene with little effect on constitutive NO synthase gene. These cytokines increased NO production, which was inhibited by L-NMMA pretreatment, and decreased alkaline phosphatase (AIPase) activity, which was not restored by L-NMMA. Furthermore, NO donors, sodium nitroprusside and NONOate dose-dependently elevated AIPase activity and expression of osteocalcin gene. These results suggest that NO directly facilitates osteoblastic differentiation and the cytokine-induced inhibition of AIPase activity is mediated via mechanism other than NO. (C) 1997 Federation of European Biochemical Societies.

    DOI: 10.1016/S0014-5793(97)00597-8

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受賞

  • 学会賞優秀発表症

    2006年   日本口腔科学会   顎下部に発生した皮下気管支性嚢胞(Subcutaneous bronchogenic cyst)の1例

    小泉 敏之

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