2023/09/01 更新

写真a

ウシジマ ヨウコ
牛島 洋子
USHIJIMA Yoko
所属
医学部附属病院 血液内科 病院講師
職名
病院講師

学位 1

  1. 博士(医学) ( 2008年5月   名古屋大学 ) 

研究分野 1

  1. ライフサイエンス / 血液、腫瘍内科学

学歴 2

  1. 名古屋大学   医学系研究科

    - 2008年5月

      詳細を見る

    国名: 日本国

  2. 名古屋大学   医学部

    - 2003年3月

      詳細を見る

    国名: 日本国

 

論文 24

  1. A case of advanced diffuse large B-cell lymphoma diagnosed from widespread superficial mycosis of the skin 査読有り 国際誌

    Suzuki Yuika, Murase Chiaki, Ushijima Yoko, Hanai Yuriko, Ogawa Yasushi, Toyama Takanori, Akiyama Masashi

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY     2023年2月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of the European Academy of Dermatology and Venereology  

    DOI: 10.1111/jdv.18937

    Web of Science

    Scopus

    PubMed

  2. Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells 査読有り 国際誌

    Kawashima Naomi, Ishikawa Yuichi, Kim Jeong Hui, Ushijima Yoko, Akashi Akimi, Yamaguchi Yohei, Hattori Hikaru, Nakashima Marie, Ikeno Seara, Kihara Rika, Nishiyama Takahiro, Morishita Takanobu, Watamoto Koichi, Ozawa Yukiyasu, Kitamura Kunio, Kiyoi Hitoshi

    NATURE COMMUNICATIONS   13 巻 ( 1 ) 頁: 1624   2022年3月

     詳細を見る

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

    Patient-derived xenografts (PDX) are widely used as human cancer models. Previous studies demonstrated clonal discordance between PDX and primary cells. However, in acute myeloid leukemia (AML)-PDX models, the significance of the clonal dynamics occurring in PDX remains unclear. By evaluating changes in the variant allele frequencies (VAF) of somatic mutations in serial samples of paired primary AML and their PDX bone marrow cells, we identify the skewing engraftment of relapsed or refractory (R/R) AML clones in 57% of PDX models generated from multiclonal AML cells at diagnosis, even if R/R clones are minor at <5% of VAF in patients. The event-free survival rate of patients whose AML cells successfully engraft in PDX models is consistently lower than that of patients with engraftment failure. We herein demonstrate that primary AML cells including potentially chemotherapy-resistant clones dominantly engraft in AML-PDX models and they enrich pre-existing treatment-resistant subclones.

    DOI: 10.1038/s41467-022-29304-6

    Web of Science

    Scopus

    PubMed

  3. Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy 査読有り

    Yamauchi Nobuhiko, Maruyama Dai, Choi Ilseung, Atsuta Yoshiko, Sakai Rika, Miyashita Kazuho, Moriuchi Yukiyoshi, Tsujimura Hideki, Kubota Nobuko, Yamamoto Go, Igarashi Tadahiko, Izutsu Koji, Yoshida Shinichiro, Kojima Kensuke, Uchida Toshiki, Inoue Yoshiko, Tsukamoto Norifumi, Ohtsuka Eiichi, Suzuki Sachiko, Inaguma Yoko, Ichikawa Satoshi, Gomyo Hiroshi, Ushijima Yoko, Nosaka Kisato, Kurata Mio, Tanaka Yasuhito, Ueda Ryuzo, Mizokami Masashi, Kusumoto Shigeru

    CANCER SCIENCE   112 巻 ( 5 ) 頁: 1943 - 1954   2021年5月

     詳細を見る

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

    We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti–HBV prophylactic therapy: no nucleos(t)ide analogue (non–NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P =.081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P <.001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non–NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P <.001). Of note, 3 non–NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.

    DOI: 10.1111/cas.14846

    Web of Science

    Scopus

    PubMed

  4. Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation 査読有り

    Goto Tatsunori, Murata Makoto, Nishida Tetsuya, Terakura Seitaro, Kamoshita Sonoko, Ishikawa Yuichi, Ushijima Yoko, Adachi Yoshiya, Suzuki Satoshi, Kato Katsuyoshi, Hirakawa Akihiro, Nishiwaki Satoshi, Nishio Nobuhiro, Takahashi Yoshiyuki, Kodera Yoshihisa, Matsushita Tadashi, Kiyoi Hitoshi

    STEM CELLS TRANSLATIONAL MEDICINE   10 巻 ( 4 ) 頁: 542 - 553   2021年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Stem Cells Translational Medicine  

    Mesenchymal stem cells (MSCs) have immunomodulatory properties and support hematopoiesis in the bone marrow (BM). To develop a new strategy to not only prevent graft-vs-host disease (GVHD) but also to enhance engraftment, a phase I trial of cord blood transplantation (CBT) combined with intra-BM injection of MSCs (MSC-CBT) was designed. Third-party BM-derived MSCs were injected intra-BM on the day of CBT. The conditioning regimen varied according to patient characteristics. GVHD prophylaxis was tacrolimus and methotrexate. The primary endpoint was toxicity related to intra-BM injection of MSCs. Clinical outcomes were compared with those of six controls who received CBT alone. Five adult patients received MSC-CBT, and no adverse events related to intra-BM injection of MSCs were observed. All patients achieved neutrophil, reticulocyte, and platelet recoveries, with median times to recoveries of 21, 35, and 38 days, respectively, comparable with controls. Grade II-IV acute GVHD developed in three controls but not in MSC-CBT patients. No patients developed chronic GVHD in both groups. At 1 year after transplantation, all MSC-CBT patients survived without relapse. This study shows the safety of MSC-CBT, and the findings also suggest that cotransplantation of MSCs may prevent GVHD with no inhibition of engraftment. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as number 000024291.

    DOI: 10.1002/sctm.20-0381

    Web of Science

    Scopus

    PubMed

  5. [A message to hematology residents in diverse career pathways]. 招待有り 査読有り

    Ushijima Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   62 巻 ( 7 ) 頁: 820 - 829   2021年

     詳細を見る

    担当区分:筆頭著者   記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11406/rinketsu.62.820

    PubMed

  6. Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific Molecular Features 査読有り

    Nishiwaki Satoshi, Kim Jeong Hui, Ito Masafumi, Maeda Matsuyoshi, Okuno Yusuke, Koyama Daisuke, Ozawa Yukiyasu, Gunji Masaharu, Osaki Masahide, Kitamura Kunio, Ushijima Yoko, Ishikawa Yuichi, Miyamura Koichi, Sugiura Isamu, Kiyoi Hitoshi

    FRONTIERS IN ONCOLOGY   10 巻   頁: 586567   2020年10月

     詳細を見る

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

    Background: Recently, various blood cell lineages expressing the BCR-ABL fusion gene in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have been reported. However, the biological and clinical significance of these BCR-ABL lineages has not been established; therefore, we aimed to clarify the impacts of these different BCR-ABL-expressing lineages. Patients: Multi-lineage BCR-ABL expression (multi-Ph) was defined as BCR-ABL expression outside of the B-lineage compartment, as determined by fluorescence in situ hybridization (FISH) in peripheral blood neutrophils and bone marrow clots, and flow cytometry-sorted polymerase chain reaction (PCR). We analyzed IKZF1 deletion patterns by PCR, examined gene expression profiles using RNA sequencing, and compared treatment outcomes across different BCR-ABL-expressing lineages. Results: Among the 21 multi-Ph patients in our 59-patient cohort (36%), BCR-ABL expression was detected at the multipotential progenitor level. However, no IKZF1 deletion patterns or gene expression profiles were identified that were specific for multi-Ph. However, multi-Ph patients were found to have better survival rates than patients with uni-lineage BCR-ABL expression [event-free survival (EFS): 74 vs. 33%, P = 0.01; overall survival (OS): 79 vs. 44% at 4 years, P = 0.01]. In multivariate analyses, multi-Ph was identified as a good prognostic factor for both EFS and OS. Conclusion: We confirmed that more than one-third of Ph+ALL patients could be classified as mutli-Ph. Although no specific molecular characteristics were identified for multi-Ph, this phenotype was associated with better treatment outcomes.

    DOI: 10.3389/fonc.2020.586567

    Web of Science

    Scopus

    PubMed

  7. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial 査読有り 国際誌

    Watanabe T., Tobinai K., Wakabayashi M., Morishima Y., Kobayashi H., Kinoshita T., Suzuki T., Yamaguchi M., Ando K., Ogura M., Taniwaki M., Uike N., Yoshino T., Nawano S., Terauchi T., Hotta T., Nagai H., Tsukasaki K., Kurosawa M., Yamagishi K., Kobayashi N., Minauchi K., Harigae H., Fukuhara N., Takahashi N., Kameoka Y., Matsuda S., Saitoh Y., Tsukamoto N., Yokohama A., Kubota N., Minami Y., Yamauchi N., Kumagai K., Tsujimura H., Izutsu K., Maruyama D., Takayama N., Ohyashiki K., Akahane D., Shimoyama T., Shimada T., Kamiyama Y., Dobashi N., Wasada I., Sano F., Takimoto M., Chou T., Ishiguro T., Masaki Y., Yamauchi T., Ono T., Yamamoto K., Kato H., Tokunaga T., Shimada K., Ushijima Y., Iida S., Kusumoto S., Uchida T., Hanamura I., Kanasugi J., Kagami Y., Hiraga J., Miyazaki K., Utsumi T., Kuroda J., Kobayashi T., Matsumura I., Rai S., Murayama T., Gomyo H., Sunami K., Makita M., Ichinohe T., Fukushima N., Yoshida I., Yakushijin Y., Asai H., Suehiro Y., Choi I., Takamatsu Y., Sasaki H., Yamasaki S., Tsukada J., Morimoto H., Kimura S., Yokoo M., Yoshida S., Moriuchi Y., Miyazaki Y., Imaizumi Y., Jo T., Nosaka K., Tatetsu H., Hidaka M., Harada N., Ohtsuka E., Ishitsuka K., Yoshimitsu M.

    The Lancet Haematology   5 巻 ( 11 ) 頁: e520 - e531   2018年11月

     詳細を見る

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

    Background: Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods: In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings: Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation: R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding: National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

    DOI: 10.1016/S2352-3026(18)30155-8

    Scopus

  8. Identification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemia 査読有り

    Hattori Hikaru, Ishikawa Yuichi, Kawashima Naomi, Akashi Akimi, Yamaguchi Yohei, Harada Yasuhiko, Hirano Daiki, Adachi Yoshiya, Miyao Kotaro, Ushijima Yoko, Terakura Seitaro, Nishida Tetsuya, Matsushita Tadashi, Kiyoi Hitoshi

    PLOS ONE   13 巻 ( 10 ) 頁: e0204850   2018年10月

     詳細を見る

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

    All-Trans retinoic acid (ATRA) and arsenic trioxide (ATO) are essential for acute promyelocytic leukemia (APL) treatment. It has been reported that mutations in PML-RARA confer resistance to ATRA and ATO, and are associated with poor prognosis. Although most PMLRARA mutations were point mutations, we identified a novel seven amino acid deletion mutation (p.K227-T233del) in the RARA region of PML-RARA in a refractory APL patient. Here, we analyzed the evolution of the mutated clone and demonstrated the resistance of the mutated clone to retinoic acid (RA). Mutation analysis of PML-RARA was performed using samples from a chemotherapy-and ATRA-resistant APL patient, and the frequencies of mutated PML-RARA transcript were analyzed by targeted deep sequencing. To clarify the biological significance of the identified PML-RARA mutations, we analyzed the ATRAinduced differentiation and PML nuclear body formation in mutant PML-RARA-Transduced HL-60 cells. At molecular relapse, the p.K227-T233del deletion and the p.R217S pointmutation in the RARA region of PML-RARA were identified, and their frequencies increased after re-induction therapy with another type of retinoiec acid (RA), tamibarotene. In deletion PML-RARA-Transduced cells, the CD11b expression levels and NBT reducing ability were significantly decreased compared with control cells and the formation of PML nuclear bodies was rarely observed after RA treatment. These results indicate that this deletion mutation was closely associated with the disease progression during RA treatment.

    DOI: 10.1371/journal.pone.0204850

    Web of Science

    Scopus

    PubMed

  9. Mutation analysis of therapy-related myeloid neoplasms 査読有り

    Nishiyama Takahiro, Ishikawa Yuichi, Kawashima Naomi, Akashi Akimi, Adachi Yoshiya, Hattori Hikaru, Ushijima Yoko, Kiyoi Hitoshi

    CANCER GENETICS   222 巻   頁: 38 - 45   2018年4月

     詳細を見る

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

    We analyzed the genetic mutation status of 13 patients with therapy-related myeloid neoplasms (t-MN). Consistent with previous reports, t-MN cells preferentially acquired mutations in TP53 and epigenetic modifying genes, instead of mutations in tyrosine kinase and spliceosome genes. Furthermore, we compared the mutation status of three t-MN cells with each of the initial lymphoid malignant cells, and identified common mutations among t-MN and the initial malignant cells in two patients. In a patient who developed chronic myelomonocytic leukemia (CMML) after follicular lymphoma (FL), TET2 mutation was identified in both CMML and FL cells. Notably, the TET2 mutation was also identified in peripheral blood cells in the disease-free period with the same allelic frequency as CMML and FL cells, but not in a germ-line control, indicating that the TET2 mutation occurred somatically in the initiating clone for both malignant cells. On the other hand, a germ-line MYB mutation was identified in a patient who developed myelodysplastic syndromes (MDS) after FL. These results suggest that germ-line deposition and clonal hematopoiesis are closely associated with t-MN susceptibility; however, further analysis is necessary to clarify the mechanism required to provide the initiating clone with lineage commitment and clonal expansion.

    DOI: 10.1016/j.cancergen.2018.02.006

    Web of Science

    Scopus

    PubMed

  10. Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol 査読有り

    Goto Tatsunori, Murata Makoto, Terakura Seitaro, Nishida Tetsuya, Adachi Yoshiya, Ushijima Yoko, Shimada Kazuyuki, Ishikawa Yuichi, Hayakawa Fumihiko, Nishio Nobuhiro, Nishiwaki Satoshi, Hirakawa Akihiro, Kato Katsuyoshi, Takahashi Yoshiyuki, Kiyoi Hitoshi

    MEDICINE   97 巻 ( 17 ) 頁: e0449   2018年4月

     詳細を見る

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

    Introduction: Delayed hematological recovery, graft failure, and acute graft-versus-host disease (GVHD) still remain major problems in cord blood transplantation (CBT). Mesenchymal stem cells (MSCs) are known to support bone marrow stroma and promote hematopoiesis. Additionally, MSCs possess immunomodulatory properties and are used clinically for the treatment of acute GVHD. Therefore, the use of MSCs to enhance engraftment and prevent GVHD after allogeneic hematopoietic cell transplantation has been explored. Recent clinical trials have shown the feasibility and safety of intravenous cotransplantation of MSCs with cord blood cells in pediatric patients, but not in adult patients, who are at greater risk of graft failure. As for the route of administration of MSCs, direct intrabone marrow injection of MSCs is thought to enhance the engraftment of cord blood cells more than intravenous injection. Based on these background findings, this clinical trial was designed to develop a new strategy to enhance engraftment and prevent GVHD after CBT. Methods and analysis: This is a single-center, phase I, clinical study to evaluate the safety of CBT combined with intrabone marrow injection of ex vivo expanded MSCs from bone marrow of a third-party donor. Adult patients with hematological disorders are eligible for this study. The target sample size is 5, and the registration period is 3 years. The target dose of MSCs infused is 0.5 × 10 6 cells/kg of patient body weight. On the day of CBT, MSCs are injected into the intrabone marrow of the patient 4 hours before the infusion of a single cord blood unit. The conditioning regimen varies according to patient age and disease. GVHD prophylaxis consists of a combination of tacrolimus and methotrexate. The primary endpoint of this study is infusional toxicity of MSCs within 14 days after transplantation.

    DOI: 10.1097/MD.0000000000010449

    Web of Science

    Scopus

    PubMed

  11. Phase II study of intrabone single unit cord blood transplantation for hematological malignancies 査読有り

    Murata Makoto, Maeda Yoshinobu, Masuko Masayoshi, Onishi Yasushi, Endo Tomoyuki, Terakura Seitaro, Ishikawa Yuichi, Iriyama Chisako, Ushijima Yoko, Goto Tatsunori, Fujii Nobuharu, Tanimoto Mitsune, Kobayashi Hironori, Shibasaki Yasuhiko, Fukuhara Noriko, Inamoto Yoshihiro, Suzuki Ritsuro, Kodera Yoshihisa, Matsushita Tadashi, Kiyoi Hitoshi, Naoe Tomoki, Nishida Tetsuya

    CANCER SCIENCE   108 巻 ( 8 ) 頁: 1634 - 1639   2017年8月

     詳細を見る

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

    The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase II study, 21 adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR ≥4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 × 107/kg (range, 2.0–4.9 × 107/kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was given after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils ≥0.5 × 109/L, reticulocytes ≥1%, and platelets ≥20 × 109/L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II–IV and III–IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study showed the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy. This study was registered with UMIN-CTR, number 000000865.

    DOI: 10.1111/cas.13291

    Web of Science

    Scopus

    PubMed

  12. Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies. 査読有り

    Tobinai K, Ogura M, Ishizawa K, Suzuki T, Munakata W, Uchida T, Aoki T, Morishita T, Ushijima Y, Takahara S

    International journal of hematology   103 巻 ( 1 ) 頁: 86 - 94   2016年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Hematology  

    In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton’s tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42–78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20 % patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3 % (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. Clinical trial registration: NCT01704963.

    DOI: 10.1007/s12185-015-1900-3

    Scopus

    PubMed

  13. The features of clearance in recombinant factor IX (BeneFIX (R)) 査読有り

    Suzuki N., Takedani H., Hirakawa A., Ushijima Y., Matsushita T.

    HAEMOPHILIA   21 巻 ( 5 ) 頁: 702 - 707   2015年9月

     詳細を見る

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

    Introduction: Dosage adjustment is very important to perform continuous infusion (CI) of recombinant factor IX (rFIX) concentrates more effectively and economically, and clearance (CL) is strongly related to the infusion rate. However, previous reports have shown that the CL of rFIX concentrates varies widely (4.2-11.4 mL kg-1 h-1). Aim: The goal of this study was to gain a better understanding of the CL of the rFIX concentrate (BeneFIX®) to precisely set the infusion rate of rFIX concentrates. Methods: We estimated CLs by five different calculation approaches: from area under the blood concentration-time curve (AUC), from in vivo recovery (IVR) and half-life, from actual FIX activity value during CI, and from the simulation by one-compartment model in seven patients with haemophilia B. Results: The mean CL calculated from AUC was 3.8 ± 0.4 mL kg-1 h-1 (range = 3.3-4.3 mL kg-1 h-1). Conclusion: The mean CL calculated from IVR and distribution half-life was 4.4 ± 0.4 mL kg-1 h-1 (range = 4.0-5.1 mL kg-1 h-1). The mean CL calculated from IVR and terminal half-life was 2.1 ± 0.5 mL kg-1 h-1 (range = 1.7-2.8 mL kg-1 h-1). The mean CL during CI was 4.9 ± 0.6 mL kg-1 h-1 (range = 4.2-5.6 mL kg-1 h-1). In addition, when we simulated the theoretical CL using a one-compartment model, the adjusted mean CL during CI was 4.8 ± 0.5 mL kg-1 h-1 (range = 4.0-5.4 mL kg-1 h-1). The CL obtained from distribution half-life was comparable to the CL during CI, while the CL calculated from terminal half-life did not reflect actual CL. Further, the rFIX concentrate was characterized by a one-compartment model under certain conditions.

    DOI: 10.1111/hae.12672

    Web of Science

    Scopus

  14. Generation and characte zation of UL21-null herpes simplex virus type 1 査読有り

    Muto Yoshifumi, Goshima Fumi, Ushijima Yoko, Kimura Hiroshi, Nishiyama Yukihiro

    FRONTIERS IN MICROBIOLOGY   3 巻 ( NOV ) 頁: 394   2012年

     詳細を見る

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

    UL21 of herpes simplex virus type 1 (HSV-1) is an accessory gene that encodes a component of the tegument. Homologs of this protein have been identified in the alpha, beta, and gamma herpesvirus subfamilies, although their functions are unclear. To clarify the functions of UL21, we generated a UL21-null HSV-1 mutant. Growth analysis showed that the synthesis of infectious UL21-null HSV-1 in glial cells was delayed and that the overall yield was low. The plaque sizes of the UL21-null mutant were smaller than those of wild-type HSV-1. We identified several candidate UL21-interacting proteins, including intermediate filaments, by yeast two-hybrid screening. The distribution of glial fibrillary acidic protein (GFAP), which is the main component of intermediate filaments, was altered in UL21-null mutant-infected glial cells compared to wild-type virus-infected cells. These results will help clarify the function of UL21 and broaden our understanding of the life cycle of HSV. © 2012 Muto, Goshima, Ushijima, Kimura and Nishiyama.

    DOI: 10.3389/fmicb.2012.00394

    Web of Science

    Scopus

    PubMed

  15. Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection 査読有り

    Iwata Seiko, Yano Shoko, Ito Yoshinori, Ushijima Yoko, Gotoh Kensei, Kawada Jun-ichi, Fujiwara Shigeyoshi, Sugimoto Koichi, Isobe Yasushi, Nishiyama Yukihiro, Kimura Hiroshi

    INTERNATIONAL JOURNAL OF CANCER   129 巻 ( 9 ) 頁: 2263 - 2273   2011年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Cancer  

    Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage of caspases and polyadenosine diphosphate-ribose polymerase, increased expression of phosphorylated IκB, and decreased expression of inhibitor of apoptotic proteins were detected by immunoblotting in bortezomib-treated cell lines. We found that bortezomib induced lytic infection in EBV-positive T cell lines, although the existence of EBV did not modulate the killing effect of bortezomib. Finally, we administered bortezomib to peripheral blood mononuclear cells from five patients with EBV-associated lymphoproliferative diseases. Bortezomib had a greater killing effect on EBV-infected cells. These results indicate that bortezomib killed T or NK lymphoma cells by inducing apoptosis, regardless of the presence or absence of EBV. © 2011 UICC.

    DOI: 10.1002/ijc.25873

    Web of Science

    Scopus

    PubMed

  16. Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch 査読有り

    Ushijima Yoko, Luo Chenhong, Kamakura Maki, Goshima Fumi, Kimura Hiroshi, Nishiyama Yukihiro

    VIROLOGY JOURNAL   7 巻   頁: 179   2010年8月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Virology Journal  

    Background. Herpes simplex virus type 2 (HSV-2) is one of many viruses that exploits and modifies the cellular ubiquitin system. HSV-2 expresses the tegument protein UL56 that has been implicated in cytoplasmic transport and/or release of virions, and is a putative regulatory protein of Nedd4 ubiquitin ligase. In order to elucidate the biological function of UL56, this study examined the interaction of UL56 with the Nedd4-family ubiquitin ligase Itch and its role in the regulation of Itch. Additionally, we assessed the similarity between UL56 and regulatory proteins of Itch and Nedd4, Nedd4-family-interactins proteins (Ndfip). Results. UL56 interacted with Itch, independent of additional viral proteins, and mediated more striking degradation of Itch, compared to Nedd4. Moreover, it was suggested that the lysosome pathway as well as the proteasome pathway was involved in the degradation of Itch. Other HSV-2 proteins with PY motifs, such as VP5 and VP16, did not mediate the degradation of endogenous Itch. Ndfip1 and Ndfip2 were similar in subcellular distribution patterns to UL56 and colocalized with UL56 in co-transfected cells. Conclusions. We believe that this is the first report demonstrating the interaction of a HSV-specific protein and Itch. Thus, UL56 could function as a regulatory protein of Itch. The mechanism, function and significance of regulating Itch in HSV-2 infection remain unclear and warrant further investigation. © 2010 Ushijima et al; licensee BioMed Central Ltd.

    DOI: 10.1186/1743-422X-7-179

    Web of Science

    Scopus

    PubMed

  17. Herpes simplex virus type 2 tegument protein UL56 relocalizes ubiquitin ligase Nedd4 and has a role in transport and/or release of virions. 査読有り

    Ushijima Y, Goshima F, Kimura H, Nishiyama Y

    Virology Journal     2009年10月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/1743-422X-6-168

  18. Herpes Simplex Virus Type 2 UL56 Interacts with the Ubiquitin Ligase Nedd4 and Increases its Ubiquitination. 査読有り

    Ushijima Y, Koshizuka T, Goshima F, Kimura H, Nishiyama Y

    Journal of Virology   82 巻 ( 11 ) 頁: 5220-5233   2008年6月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1128/JVI.02515-07

  19. Microarray analysis of transcriptional responses to infection by herpes simplex virus types 1 and 2 and their US3-deficient mutants. 査読有り

    Kamakura M, Nawa A, Ushijima Y, Goshima F, Kawaguchi Y, Kikkawa F, Nishiyama Y

    Microbes and Infection   10 巻 ( 4 ) 頁: 405-413   2008年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.micinf.2007.12.019

  20. Oligonucleotide Microarray Analysis of Gene Expression Profiles followed by a Real-time RT-PCR Assay in Chronic Active Epstein-Barr Virus Infection. 査読有り

    Ito Y, Shibata-Watanabe Y, Ushijima Y, Kawada J, Nishiyama Y, Kojima S, Kimura H

    Journal of Infectious Disease   197 巻   頁: 663-666   2008年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1086/527330

  21. Non-engineered, naturally oncolytic herpes simplex virus HSV1 HF-10: applications for cancer gene therapy. 査読有り

    Nawa A, Luo C, Zhang L, Ushjima Y, Ishida D, Kamakura M, Fujimoto Y, Goshima F, Kikkawa F, Nishiyama Y

    Current Gene Therapy   8 巻 ( 3 ) 頁: 208-221   2008年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2174/156652308784746422

  22. Intercellular trafficking and cytotoxicity of recombinant HSV-1 thymidine kinase fused with HSV-2 US11 RXP repeat peptide. 査読有り

    Luo C, Nawa A, Yamauchi Y, Kohno S, Ushijima Y, Goshima F, Kikkawa F, Nishiyama Y

    Virus Genes   34 巻 ( 3 ) 頁: 263-272   2007年6月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s11262-006-0013-8

  23. Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus. 査読有り

    Ushijima Y, Luo C, Goshima F, Yamauchi Y, Kimura H, Nishiyama Y

    Microbes and Infection   9 巻 ( 2 ) 頁: 142-149   2007年2月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.micinf.2006.10.019

  24. Identification of nuclear export signal in UL37 protein of herpes simplex virus type 2. 査読有り

    Watanabe D, Ushijima Y, Goshima F, Takakuwa H, Tomita Y, Nishiyama Y

    Biochemical and biophysical research communications   276 巻 ( 3 ) 頁: 1248-1254   2000年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1006/bbrc.2000.3600

▼全件表示

書籍等出版物 4

  1. 急性リンパ性白血病(ALL)の基礎と臨床

    牛島洋子, 清井仁( 担当: 分担執筆 ,  範囲: 発症機序)

    医薬ジャーナル社  2017年1月  ( ISBN:9784753228263

     詳細を見る

    記述言語:日本語 著書種別:教科書・概説・概論

  2. 血液科研修ノート

    牛島洋子, 冨田章裕( 担当: 分担執筆 ,  範囲: バーキットリンパ腫)

    診断と治療社  2016年5月  ( ISBN:9784787821775

     詳細を見る

    記述言語:日本語 著書種別:教科書・概説・概論

  3. KEY WORD 感染症 第2版

    牛島洋子, 西山幸廣( 担当: 分担執筆 ,  範囲: 欠損ウイルス)

    先端医学社  2008年8月  ( ISBN:9784884074838

     詳細を見る

    記述言語:日本語 著書種別:教科書・概説・概論

  4. 病原細菌・ウイルス図鑑

    牛島洋子, 西山幸廣( 担当: 分担執筆 ,  範囲: 単純ヘルペスウイルス)

    北海道大学出版会  2017年11月  ( ISBN:9784832982291

     詳細を見る

    記述言語:日本語 著書種別:教科書・概説・概論

MISC 4

  1. 抗CD33抗体医薬 gemtuzumab ozogamicinの有用性

    牛島洋子, 清井仁  

    医学のあゆみ265 巻 ( 1 ) 頁: 31 - 35   2018年4月

     詳細を見る

    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

  2. 分子標的療法

    牛島洋子, 清井仁  

    日本臨床74 巻   頁: 14 - 19   2016年12月

     詳細を見る

    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

  3. T細胞性リンパ系腫瘍に対する新規薬剤導入による新たな治療展開

    牛島洋子, 山本一仁  

    血液内科62 巻 ( 1 ) 頁: 51 - 57   2011年1月

     詳細を見る

    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

  4. 単純ヘルペスウイルスの増殖と病原性発現機構

    牛島洋子, 西山幸廣  

    蛋白質核酸酵素54 巻 ( 8 ) 頁: 953 - 960   2009年6月

     詳細を見る

    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

講演・口頭発表等 4

  1. 急性骨髄性白血病

    牛島洋子、齋藤健

    第83回日本血液学会学術集会  2021年9月25日  日本血液学会

     詳細を見る

    開催年月日: 2021年9月

    記述言語:日本語  

    開催地:Web  

  2. 多様化するキャリア形成過程の中で血液専門医を目指す医師へ

    牛島洋子

    第82回日本血液学会学術集会  2020年10月10日  日本血液学会

     詳細を見る

    開催年月日: 2020年10月 - 2020年11月

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

  3. Clonal Analysis of Acute Myeloid Leukemia secondary to Myeloproliferative Neoplasms 国際会議

    59th American Society of Hematology Annual Meeting and Exposition 

     詳細を見る

    開催年月日: 2017年12月

    記述言語:英語   会議種別:ポスター発表  

    国名:アメリカ合衆国  

  4. Clonal analysis of acute myeloid leukemia transformed from myeloproliferative neoplasms

    Yoko Ushijima, Yuichi Ishikawa, Hikaru Hattori, Naomi Kawashima, Shun Fujiwara, Seitaro Terakura, Masashi Sanada, Hitoshi Kiyoi

     詳細を見る

    開催年月日: 2017年10月

    記述言語:英語   会議種別:口頭発表(一般)  

    国名:日本国  

共同研究・競争的資金等の研究課題 2

  1. シングルセルバーコードラベル化PDXモデルによる難治性造血器腫瘍クローンの選択・進展過程に関与する分子病態の解明に関する研究

    研究課題番号:21cm0106581h0001  2021年5月 - 2022年3月

    次世代がん医療創生研究事業 

      詳細を見る

    担当区分:研究分担者 

  2. 骨髄系腫瘍における難治性クローンへの進展・選択過程に生じる分子病態の解明

    研究課題番号:20cm0106562h0002  2019年8月 - 2021年3月

    次世代がん医療創生研究事業 

      詳細を見る

    担当区分:研究分担者  資金種別:競争的資金

科研費 3

  1. 難治性急性前骨髄球性白血病の分子病態解明と新規治療標的分子の探索

    研究課題/研究課題番号:23K07832  2023年4月 - 2026年3月

    科学研究費助成事業  基盤研究(C)

    牛島 洋子

      詳細を見る

    担当区分:研究代表者 

    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    急性前骨髄球性白血病(APL)は全トランスレチノイン酸および亜ヒ酸による治療導入によりその予後が著明に改善したが、高リスク群では再発例も多く存在する。これまでに申請者らは、初発時検体で免疫不全マウスへの異種移植(PDX)モデルが樹立され継代可能なAPL症例は再発を来すことを見いだした。本研究では、APL-PDXモデルで生物学的に意義付けられた難治性クローンの形成に関わる要因に着目し難治性APLの分子病態解明を図り、分子病態に基づく新規治療法を、難治性APL-PDXマウスモデルを用いて検討し、開発することを目指す。

  2. 骨髄増殖性腫瘍とその二次性白血病におけるinitiating変異の同定と機能解析

    研究課題/研究課題番号:19K08835  2019年4月 - 2022年3月

    科学研究費助成事業  基盤研究(C)

    牛島 洋子

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    フィラデルフィア染色体(Ph)陰性骨髄増殖性腫瘍(MPN)から転化した二次性急性骨髄性白血病(sAML)は治療抵抗性で急性白血病の中でも極めて予後不良である。その発生過程ではJAK2変異などのMPNドライバー変異遺伝子以外の分子の重要性が示唆されている。本研究は、MPNドライバー変異遺伝子以外の、MPN期とsAML期に共通する変異遺伝子の機能解析、および、症例検体での同遺伝子変異解析により、MPNおよびsAMLにおけるinitiating変異を同定しその機能と意義を明らかにすることを目的とする。本研究は、骨髄系腫瘍の分子基盤解明、さらに、新たな治療標的候補分子の同定につながることが期待される。
    骨髄増殖性腫瘍(MPN)から転化した二次性急性骨髄性白血病(sAML)の一部はMPNドライバー変異を欠き、MPNとsAMLに共通したinitiating変異の重要性が示唆されている。JAK2変異陰性sAML症例においてMPN期と共通して検出されたZNF143、SMARCC2、UBR4変異をinitiating変異候補として検討した。MPNおよび/またはsAML症例80例における遺伝子変異解析ではこれら変異の普遍性は示されなかった。3遺伝子変異陽性症例のsAML寛解期検体における単一細胞を用いた変異解析から、多発多段階の変異獲得によると考えられる多様な変異パターンが明らかとなった。
    本研究では、MPN-sAML症例ペア検体を含む多数症例検体における解析により、MPNおよびsAMLが症例間においても1症例内においても多彩な進展形式をとることが示され、MPNから転化したsAMLが極めて難治性で予後不良である一因と考えられた。sAMLはMPN発症から10年前後の長期間を経て生じ、また、その頻度は高くないことから、今回集積された検体は新たなアプローチによる病態解明を今後図るうえでも意義を有すると考えられる。

  3. 単純ヘルペスウイルスUL56遺伝子のユビキチンシステム制御に関する研究

    2008年 - 2009年

    科学研究費補助金 

      詳細を見る

    担当区分:研究代表者