大喜多 肇 (オオキタ ハジメ)

Okita, Hajime

写真a

所属(所属キャンパス)

医学部 病理診断部 (信濃町)

職名

准教授

外部リンク

経歴 【 表示 / 非表示

  • 2003年05月
    -
    2010年03月

    国立成育医療センター発生・分化研究部機能分化研究室

  • 2010年04月
    -
    2014年11月

    (独)国立成育医療研究センター小児血液・腫瘍研究部分子病理研究室

  • 2014年12月
    -
    継続中

    慶應義塾大学医学部病理学教室

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾大学, 課程

 

研究分野 【 表示 / 非表示

  • 人体病理学

 

論文 【 表示 / 非表示

  • Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome

    Haruta M., Arai Y., Okita H., Tanaka Y., Takimoto T., Sugino R., Yamada Y., Kamijo T., Oue T., Fukuzawa M., Koshinaga T., Kaneko Y.

    Neoplasia (United States) (Neoplasia (United States))  21 ( 1 ) 117 - 131 2019年01月

    ISSN  15228002

     概要を見る

    © 2018 The Authors To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without +12, 11q− 16q− or HACE1 loss. RFS was better for those with than those without +12 (P =.010) and worse for those with than those without 11q− 16q− or HACE1 loss (P =.001,.025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and +12 subgroup; high risk for the no +12 plus 11q− 16q− or HACE1 loss subgroup; intermediate risk for the WT1 type and no +12 plus no 11q− 16q− or HACE1 loss subgroup. Among the 27 WTs examined, the expression of 146 genes on chromosome 12 was stronger in +12 tumors than in no +12 tumors, while that of 10 genes on 16q was weaker in 16q− tumors than in no 16q− tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. +12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalities may be related to altered gene expression associated with these abnormalities.

  • A curative treatment strategy using tumor debulking surgery combined with immune checkpoint inhibitors for advanced pediatric solid tumors: An in vivo study using a murine model of osteosarcoma

    Shimizu T., Fuchimoto Y., Okita H., Fukuda K., Kitagawa Y., Ueno S., Kuroda T.

    Journal of Pediatric Surgery (Journal of Pediatric Surgery)  53 ( 12 ) 2460 - 2464 2018年12月

    ISSN  00223468

     概要を見る

    © 2018 Elsevier Inc. Background/purpose: This study aimed to assess the significance of tumor debulking surgery by using immune checkpoint inhibitors for advanced pediatric solid tumors in a murine model of advanced osteosarcoma. Methods: In C3H mice, 5 × 10 6 LM8 (osteosarcoma cell line with a high metastatic potential in the lungs originating from the C3H mouse) cells were transplanted subcutaneously. Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, n = 5), the surgery group underwent subcutaneous tumor resection (tumor debulking surgery) 11 days after transplantation (SG, n = 10), the immunotherapy group received a cocktail consisting of 200 μg each of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86) intraperitoneally on posttransplantation days 11, 14, 18, and 21 (IG, n = 10), and the combination therapy group, tumor debulking surgery on day 11 and the cocktail intraperitoneally on days 11, 14, 18, and 21 (COMBG, n = 10). Survival curves were plotted by using the Kaplan–Meier method and compared with those plotted using the log-rank test. Next, the lungs of mice in the 4 groups were pathologically evaluated. Results: The COMBG showed significantly longer survival than the other three groups (P ≤ 0.002), whereas the SG and IG revealed no difference in survival rate compared to CG. Pathological evaluations revealed no lung metastasis 16 weeks after tumor transplantation in the survivors of COMBG. Conclusions: The results of this study suggest that tumor debulking surgery combined with immune checkpoint inhibitors could be a curative treatment for advanced pediatric solid tumors.

  • Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA

    Ueno-Yokohata H., Okita H., Nakasato K., Hishiki T., Shirai R., Tsujimoto S., Osumi T., Yoshimura S., Yamada Y., Shioda Y., Kiyotani C., Terashima K., Miyazaki O., Matsumoto K., Kiyokawa N., Yoshioka T., Kato M.

    Genes Chromosomes and Cancer (Genes Chromosomes and Cancer)  57 ( 10 ) 525 - 529 2018年10月

    ISSN  1045-2257

     概要を見る

    © 2018 Wiley Periodicals, Inc. Clear cell sarcoma of the kidney (CCSK) is the second most common renal malignancy in children. The prognosis is poorer in CCSK than in Wilms’ tumor, and multimodal treatment including surgery, intensive chemotherapy, and radiation is required to improve the outcome for children with CCSK. Histological evaluation is required for the diagnosis. However, biopsies of tumors to obtain diagnostic specimens are not routinely performed because of the risk of spreading tumor cells during the procedure. Recently, internal tandem duplication (ITD) of BCOR has been recognized as a genetic hallmark of CCSK. We herein established a novel BCOR-ITD-specific polymerase chain reaction method with well-designed primers, and then performed a liquid biopsy for cell-free DNA (cfDNA) obtained from plasma of three children with nonmetastatic renal tumors (stage II) and from one control. BCOR-ITD was positively detected in the cfDNA of two cases, both of which were later diagnosed as CCSK based on histological feature of the resected tumor specimen, while it was not detected for a normal control and a patient diagnosed with Wilms’ tumor. Our study is the first one of preoperative circulating tumor DNA assay in pediatric renal tumors. The liquid biopsy method enables less invasive, preoperative diagnosis of CCSK with no risk of tumor spillage, which can avoid iatrogenic upstaging.

  • Outcome of renal tumors registered in Japan Wilms Tumor Study-2 (JWiTS-2): A report from the Japan Children's Cancer Group (JCCG)

    Koshinaga T., Takimoto T., Oue T., Okita H., Tanaka Y., Nozaki M., Tsuchiya K., Inoue E., Haruta M., Kaneko Y., Fukuzawa M.

    Pediatric Blood and Cancer (Pediatric Blood and Cancer)  65 ( 7 ) e27056 2018年04月

    ISSN  1545-5017

     概要を見る

    © 2018 Wiley Periodicals, Inc. Background: Japan Wilms Tumor Study-2 (JWiTS-2) mandated central pathology review for all case registrations. The study aimed to compare the outcomes of patients with unilateral Wilms tumor enrolled on the JWiTS-1 and JWiTS-2 trials. Procedure: The JWiTS-2 trial (2006–2014), a prospective, single-arm study, required compulsory submission of histologic slides to central pathology, while in the JWiTS-1 trial, such submission was not compulsory. Relapse-free survival (RFS) and overall survival (OS) versus cases in the JWiTS-1 trial (1996–2005) were statistically evaluated. Results: Of 277 enrolled patients with primary renal tumors diagnosed by the central pathology review system, 225 patients with unilateral renal tumors were followed up over 9 years. The RFS and OS of Wilms tumor (n = 178) were 90.4% (P = 0.0003) and 96.8% (P = 0.054), respectively, as compared to 74.9% and 89.4% in JWiTS-1. RFS rates of stages I–III Wilms tumor in JWiTS-2 were more than 90%, although the outcome of stage IV Wilms tumor was significantly poorer (RFS: 66.2%) (P = 0.0094). RFS and OS of clear cell sarcoma of the kidney (CCSK; n = 31) were 82.4% (P = 0.30) and 91.3% (P = 0.42), respectively, as compared to 68.8% and 81.3% in JWiTS-1, and those of rhabdoid tumor of the kidney (RTK; n = 16) were 18.8% (P = 0.88) and 25.0% (P = 0.80), respectively, as compared to 23.5% and 23.5% in JWiTS-1. Conclusions: RFS and OS for stages I–III Wilms tumor were improved in JWiTS-2 compared to JWiTS-1, whereas outcomes for stage IV Wilms tumor, CCSK, and RTK did not improve.

  • The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma

    Shimizu, T., Fuchimoto, Y., Fukuda, K., Okita, H., Kitagawa, Y. and Kuroda, T.

    J Pediatr Surg 52 ( 12 ) 2047 - 2050 2017年12月

    ISSN  1531-5037

     概要を見る

    BACKGROUND/PURPOSE: The prognosis of patients with metastases remains unsatisfactory in certain pediatric solid tumors. In this study, we evaluated the efficacy of immune checkpoint inhibitors against such metastases using a murine model of osteosarcoma. METHODS: Murine osteosarcoma LM8 cells were transplanted subcutaneously into C3H mice. The primary tumor lesion was surgically resected 11 days after transplantation. Two hundred micrograms of three antibodies (anti-PD-1, anti-PD-L1, and anti-OX-86) or an isotype antibody were administered intraperitoneally on post-transplantation days 11, 14, 18, and 21. Survival curves were plotted by the Kaplan-Meier method and compared with the log-rank test. Computed tomography (CT) scans were performed on day 11 after tumor transplantation (pre-therapy) and on day 25 (post-therapy). For pathology, 3 mice from each group were euthanized on days 11, 22, and 33 after tumor transplantation. RESULTS: The antibody-treated group had a significantly longer survival time compared with the control group (p = 0.002). Both the CT scan and pathological results revealed suppression of metastatic tumor proliferation in the treatment group as compared with the control group. CONCLUSIONS: These results suggest that immune checkpoint inhibitors may be an innovative therapy for lung metastases of advanced pediatric solid tumors.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

研究発表 【 表示 / 非表示

  • Bcl-2関連遺伝子EATのトランスジェニック・マウスでは,多彩な腫瘍が発生する

    大喜多肇,梅澤明弘,松下健一,鈴木淳,下田耕治,福間真理子,佐野誠,山田健人,秦順一

    第90回日本病理学会総会, 2001年04月

  • Bcl-2関連遺伝子EATのトランスジェニック・マウスでは多彩な腫瘍が発生する

    大喜多肇,梅澤明弘,松下健一,鈴木淳,下田耕二,福間真理子,佐野誠,山田健人,秦順一

    第59回日本癌学会総会, 2000年10月

  • Molecular analysis of the Ewing family of tumors in japan:EWS/ETS fusion genes are availablefor diagnosis

    Okita H, Umezawa A, Urano F, Yabe H, Fukuma M, Hata J

    Interanational Congress of the international Academy of Pathology, 2000年10月

  • Islet cells hyperplasia/Adenoma in the EAT transgenic mice

    Umezawa A, Matsusita K, Okita H, Suzuki A, Ando T, Shimoda K, Sano M, Fukuma M, Yamada T, Urano F, Hata J

    International Congress of the International Academy of Pathology, 2000年10月

  • EAT/(Bcl-2関連遺伝子)トランスジェニック・マウスにおける膵ラ氏島の過形成及び腺腫

    大喜多肇,梅澤明弘,松下健一,鈴木淳,下田耕二,福間真理子,佐野誠,山田健人,秦順一

    第89回日本病理学会, 2000年04月

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競争的資金等の研究課題 【 表示 / 非表示

  • エピゲノム修飾因子の機能解析による小児固形腫瘍の発症機構解明

    2016年04月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 大喜多 肇, 基盤研究(C), 補助金,  代表

 

担当授業科目 【 表示 / 非表示

  • 病理学総論

    2021年度

  • 病理学各論

    2021年度

  • 病理診断実習

    2021年度

  • 病理学総論

    2020年度

  • 病理学各論

    2020年度

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