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李 政樹リ マサキ

所属部署医学研究科血液・腫瘍内科学分野
職名講師
メールアドレス
ホームページURLhttp://ncu-ketsuekishuyo.jp/
生年月日
Last Updated :2020/05/26

研究者基本情報

基本情報

    ORCID ID:0000-0002-9617-486X

研究活動情報

研究キーワード

    小胞体ストレス, 耐性, 多発性骨髄腫, 分子標的薬

論文

  • Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) Tax-specific T-cell exhaustion in HTLV-1-infected individuals., Masaki A, Ishida T, Suzuki S, Ito A, Narita T, Kinoshita S, Ri M, Kusumoto S, Komatsu H, Inagaki H, Ueda R, Iida S, Cancer science, 109, (8) 2383 - 2390,   2018年08月, 査読有り
  • Cyclin-dependent kinase 9 as a potential specific molecular target in NK cell leukemia/lymphoma., Kinoshita S, Ishida T, Ito A, Narita T, Masaki A, Suzuki S, Yoshida T, Ri M, Kusumoto S, Komatsu H, Shimizu N, Inagaki H, Kuroda T, Scholz A, Ueda R, Sanda T, Iida S, Haematologica,   2018年08月, 査読有り
  • Potent antitumor effect of combination therapy with sub-optimal doses of Akt inhibitors and pomalidomide plus dexamethasone in multiple myeloma., Kinoshita S, Ri M, Kanamori T, Aoki S, Yoshida T, Narita T, Totani H, Ito A, Kusumoto S, Ishida T, Komatsu H, Iida S, Oncology letters, 15, (6) 9450 - 9456,   2018年06月, 査読有り
  • A Phase I/II Study for Dose-finding, and to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of NK012, an SN-38-Incorporating Macromolecular Polymeric Micelle, in Patients with Multiple Myeloma., Ri M, Suzuki K, Iida S, Hatake K, Chou T, Taniwaki M, Watanabe N, Tsukamoto T, Internal medicine (Tokyo, Japan), 57, (7) 939 - 946,   2018年04月, 査読有り
  • Potent anti-tumor activity of a syringolin analog in multiple myeloma: a dual inhibitor of proteasome activity targeting β2 and β5 subunits., Yoshida T, Ri M, Kanamori T, Aoki S, Ashour R, Kinoshita S, Narita T, Totani H, Masaki A, Ito A, Kusumoto S, Ishida T, Komatsu H, Kitahata S, Chiba T, Ichikawa S, Iida S, Oncotarget, 9, (11) 9975 - 9991,   2018年02月, 査読有り
  • Clinical significance of tryptophan catabolism in Hodgkin lymphoma., Masaki A, Ishida T, Maeda Y, Ito A, Suzuki S, Narita T, Kinoshita S, Takino H, Yoshida T, Ri M, Kusumoto S, Komatsu H, Inagaki H, Ueda R, Choi I, Suehiro Y, Iida S, Cancer science, 109, (1) 74 - 83,   2018年01月, 査読有り
  • [Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance mimicking POEMS syndrome]., Kanamori T, Kusumoto S, Okita K, Hagiwara S, Kato C, Nakashima T, Murakami S, Narita T, Ito A, Ri M, Ishida T, Komatsu H, Matsukawa N, Iida S, [Rinsho ketsueki] The Japanese journal of clinical hematology, 59, (2) 161 - 166,   2018年, 査読有り
  • Anaplastic multiple myeloma: possible limitations of conventional chemotherapy for long-term remission., Ichikawa S, Fukuhara N, Hatta S, Himuro M, Nasu K, Ono K, Okitsu Y, Kobayashi M, Onishi Y, Ri M, Ichinohasama R, Harigae H, Journal of clinical and experimental hematopathology : JCEH, 58, (1) 39 - 42,   2018年, 査読有り
  • Low expression of neural cell adhesion molecule, CD56, is associated with low efficacy of bortezomib plus dexamethasone therapy in multiple myeloma., Yoshida T, Ri M, Kinoshita S, Narita T, Totani H, Ashour R, Ito A, Kusumoto S, Ishida T, Komatsu H, Iida S, PloS one, 13, (5) ,   2018年, 査読有り
  • [Role of novel proteasome inhibitors in the treatment of relapsed/refractory multiple myeloma]., Ri M, [Rinsho ketsueki] The Japanese journal of clinical hematology, 59, (10) 2162 - 2168,   2018年, 査読有り
  • Efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells for autologous transplantation in Japanese patients with multiple myeloma, Masaki Ri, Kosei Matsue, Kazutaka Sunami, Chihiro Shimazaki, Akio Hayashi, Yoshinori Sunaga, Toru Sasaki, Kenshi Suzuki, INTERNATIONAL JOURNAL OF HEMATOLOGY, 106, (4) 562 - 572,   2017年10月, 査読有り, To evaluate the efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells (HSCs) for autologous transplantation in Japanese patients with multiple myeloma (MM). In a randomized study, patients received G-CSF (filgrastim, 400 A mu g/m(2)/day) for 4 days prior to the first dose of plerixafor. Starting on Day 4 evening and for up to 4 days, patients received either plerixafor (240 A mu g/kg/day) + G-CSF group (PG group) or G-CSF alone (G group). Daily apheresis started on Day 5 for up to 4 days, or until ae<yen>6 x 10(6) CD34+ cells/kg were collected. A total of 7 patients were randomized in each treatment group. Five patients in PG group and no patients in G group achieved a collection of ae<yen>6 x 10(6) CD34+ cells/kg in ae<currency>2 days of apheresis [difference of 71.4% (90%CI 29-100%)]. These results were supported by the shorter median time to collect ae<yen>6 x 10(6) CD34+ cells/kg (2 days in PG group; no patient in G group). The incidence of treatment emergent adverse events (TEAEs) was higher in PG group than in G group. Plerixafor was well tolerated, and effective for the mobilization/collection of peripheral HSCs for autologous transplantation in Japanese patients with MM.
  • Safety and efficacy of daratumumab in Japanese patients with relapsed or refractory multiple myeloma: a multicenter, phase 1, dose-escalation study, Shinsuke Iida, Kenshi Suzuki, Shigeru Kusumoto, Masaki Ri, Nobuhiro Tsukada, Yu Abe, Masayuki Aoki, Mitsuo Inagaki, INTERNATIONAL JOURNAL OF HEMATOLOGY, 106, (4) 541 - 551,   2017年10月, 査読有り, Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ae<yen>20 years) with ae<yen>2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity. Daratumumab was well-tolerated. Eight patients experienced Grade ae<yen>3 adverse event (AE). Four serious AEs were observed in three patients; no AEs leading to death. Infusion-related reactions occurred in four (44%) patients and were Grade 1 or 2. Mean (SD) cumulative dose of daratumumab was 132.3 (108.5) mg/kg. Median duration of follow-up was 10.5 months (range 2.3, 16.4) for 8 mg/kg cohort and 9.9 months (range 1.7, 13.2) for 16 mg/kg cohort. The ORR (44%) comprised 1 and 3 partial responses in 8 and 16 mg/kg cohorts, respectively. The median PFS was 6 months for 8 mg/kg cohort, 9.5 months for 16 mg/kg cohort. Daratumumab serum exposure was increased with increasing dose. Antibodies against daratumumab were not observed. Daratumumab was safe and well-tolerated in Japanese patients with relapsed /refractory MM.
  • Novel monitoring of hepatitis B reactivation based on ultra-high sensitive hepatitis B surface antigen assay, Noboru Shinkai, Shigeru Kusumoto, Shuko Murakami, Shintaro Ogawa, Masaki Ri, Tekeshi Matsui, Akihiro Tamori, Hidenori Toyoda, Takashi Ishida, Shinsuke Iida, Yasuhito Tanaka, LIVER INTERNATIONAL, 37, (8) 1138 - 1147,   2017年08月, 査読有り, Background & Aims: Occult hepatitis B virus (HBV) infection should be evaluated before systemic chemotherapy to prevent HBV reactivation-related hepatitis. We investigated HBV reactivation using high sensitivity HB surface antigen (HBsAg) chemiluminescent enzyme immunoassay (HBsAg-HQ) and ultra-high sensitive HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA). Methods: Of 120 HBV-resolved patients with haematological malignancy receiving systemic chemotherapy from 2012 to 2015 in our hospital, 13 patients had HBV DNA reactivation (in 12/13 patients HBV DNA became quantifiable) according to HBV DNA monitoring. These patients were applied for Architect HBsAg-QT (detection limit: 50 mIU/mL), HBsAg-HQ (5 mIU/mL) and ICT-CLEIA (0.5 mIU/mL) using stored samples. Results: When HBV DNA was firstly quantifiable by regular HBV DNA monitoring, HBsAg-QT was detected in 1/12 patients (8%), HBsAg-HQ was detected in 4/12 patients (33%) and ICT-CLEIA was detected in all 12 patients (100%), suggesting that the sensitivity of ICT-CLEIA was comparable to that of HBV DNA quantification. Interestingly, two patients were HBsAg positive by ICT-CLEIA before HBV DNA became detectable. Median difference of detectable point between HBV DNA and ICT-CLEIA was zero (range from -28 to 56 days), while median delay by HBsAg-QT or HBsAg-HQ was 52.5 days after HBV DNA became detectable. Although anti-HBs titres were high (131.9 mIU, 80.4 mIU) in two patients with escape mutations (Saa126V, Saa145R), HBsAg by ICT-CLEIA and HBV DNA were detectable concurrently. Conclusions: ICT-CLEIA is a novel assay for HBV monitoring to prevent hepatitis caused by HBV reactivation.
  • Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma, Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda, BRITISH JOURNAL OF HAEMATOLOGY, 178, (4) 534 - 546,   2017年08月, 査読有り, Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells. Introduction of miR-375 reduced PDPK1 expression in human myeloma cell lines (HMCLs), indicating that miR-375 is the dominant regulator of PDPK1 expression. In addition, miR-375 introduction also downregulated IGF1R and JAK2 in HMCLs. CpG islands in the MIR375 promoter were pathologically hypermethylated in all 8 HMCLs examined and in most of 58 patient-derived myeloma cells. Treatment with SGI-110, a hypomethylating agent, and/or trichostatin A, a histone deacetylase inhibitor, increased miR-375 expression, but repressed PDPK1, IGF1R and JAK2 in HMCLs. Collectively, these results show the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways.
  • Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma, Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Akifumi Takaori-Kondo, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida, BLOOD, 130, (9) 1114 - 1124,   2017年08月, 査読有り, Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). The deregulation of CDK9/PTEFb has important implications for many cancer types. BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase 1 studies. Weevaluated the therapeutic potential ofBAY1143572 in adult T-cell leukemia/lymphoma (ATL). As a result of CDK9 inhibition and subsequent inhibition of phosphorylation at serine 2 of the RNAPII CTD, BAY1143572 decreased c-Mycand Mcl-1 levels in ATL-derived or human T-cell lymphotropic virus type-1 (HTLV-1)-transformed lines and primary ATL cells tested, leading to their growth inhibition and apoptosis. Median inhibitory concentrations for BAY 1143572 in ATL-derived or HTLV-1-transformed lines (n = 8), primary ATL cells (n=11), and CD4 1 cells fromhealthy volunteers (n=5) were 0.535, 0.30, and 0.36 mM, respectively. Next, NOG mice were used as recipients of tumor cells from an ATL patient. BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both). BAY 1143572-treated ATL-bearingmice demonstrated significantly prolonged survival compared with untreated ATL-bearing mice (n=7 for both). Collectively, this study indicates thatBAY1143572showedstrongpotential as anovel treatmentof ATL.
  • Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan., Suzuki K, Ri M, Chou T, Sugiura I, Takezako N, Sunami K, Ishida T, Izumi T, Ozaki S, Shumiya Y, Ota K, Iida S, Cancer science, 108, (3) 461 - 468,   2017年03月, 査読有り
  • Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma, Masaki Ri, INTERNATIONAL JOURNAL OF HEMATOLOGY, 104, (3) 273 - 280,   2016年09月, 査読有り, Bortezomib (BTZ), a proteasome inhibitor, was initially reported as an inhibitor of the NF-kappa B pathway, which plays a critical role in the pathogenesis of multiple myeloma (MM). The NF-kappa B activity of MM cells is mediated via two distinct pathways, canonical and non-canonical, which show opposing activity after BTZ treatment in MM cells. Recent studies of proteasome inhibition in MM cells reveal that the accumulation of unfolded proteins in the endoplasmic reticulum (ER), referred to as ER stress, triggered the activity of several pro-apoptotic factors and sources of cell stress, such as the accumulation of reactive oxygen species (ROS), which is considered to be the main mechanism of action of BTZ-induced apoptosis. Several factors associated with ER stress and unfolded protein response (UPR) have been identified with the sensitivity of BTZ treatment. Low levels of XBP1, ATF3, and ATF4, which regulate UPR and ER stress-induced apoptosis, have been observed in poor responders to BTZ treatment, and three other genes, KLF9, Nampt, and CDK5, are associated with response to BTZ-containing therapy. These findings contribute to a better understanding of the mechanisms underlying BTZ-induced apoptosis in MM cells; however, further study is needed to develop potential predictive biomarkers of efficacy of BTZ-containing therapy.
  • The value of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker for hepatitis C virus-related complications after systemic chemotherapy, Haruhito Totani, Shigeru Kusumoto, Yasuhito Tanaka, Nana Suzuki, Shinya Hagiwara, Shiori Kinoshita, Etsuko Iio, Asahi Ito, Masaki Ri, Takashi Ishida, Hirokazu Komatsu, Shinsuke Iida, INTERNATIONAL JOURNAL OF HEMATOLOGY, 104, (3) 384 - 391,   2016年09月, 査読有り, Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) was developed recently as a predictive marker of progression to liver fibrosis and hepatocellular carcinoma (HCC) in patients seropositive for hepatitis C virus (HCV). We retrospectively analyzed 16 HCV-seropositive patients who received systemic chemotherapy for hematologic malignancies to evaluate the usefulness of WFA(+)-M2BP for predicting HCV-related complications. These were defined as the onset of significant liver damage (LD) with increased HCV RNA levels, leading to interrupted or discontinued chemotherapy or the occurrence of HCC after chemotherapy. Baseline WFA(+)-M2BP levels were determined using preserved serum samples. The median level of WFA(+)-M2BP was 1.59 [cutoff index (C.O.I.) value range 0.38-6.66]. With a median follow-up of 623 days (range 120-2404), LD and HCC were observed in three and two patients, respectively. Detectable HCV RNA and WFA(+)-M2BP aeyen2.0 C.O.I. at baseline were identified as risk factors for these HCV-related complications (P = 0.034 and P = 0.005, respectively). The sensitivity, specificity, and positive and negative predictive values of the WFA(+)-M2BP level (cutoff point: 2.0 C.O.I.) for the occurrence of HCV-related complications were 100.0, 81.8, 71.4, and 100.0 %, respectively. WFA(+)-M2BP may be a useful marker for the prediction of HCV-related complications in HCV-seropositive patients following systemic chemotherapy.
  • Design, Synthesis, and Biological Activity of Isosyringolin A, Shun Kitahata, Takuya Chiba, Takashi Yoshida, Masaki Ri, Shinsuke Iida, Akira Matsuda, Satoshi Ichikawa, ORGANIC LETTERS, 18, (9) 2312 - 2315,   2016年05月, 査読有り, Isosyringolin A, which is an isomer of the proteasome-inhibiting natural product syringolin A, was designed and synthesized to develop analogues that are step economical and synthetically accessible in a practical manner. It was revealed that isosyringolin A exhibited proteasome-inhibitory activity comparable to that of syringolin A and that its derivatization leads to great enhancement in its proteasome inhibitory activity as well as its cytotoxicity against human myeloma cells.
  • Mechanism of action and determinants of sensitivity to the proteasome inhibitor bortezomib in multiple myeloma therapy., Ri M, [Rinsho ketsueki] The Japanese journal of clinical hematology, 57, (5) 537 - 545,   2016年05月, 査読有り
  • Phase I study of once weekly treatment with bortezomib in combination with lenalidomide and dexamethasone for relapsed or refractory multiple myeloma, Haruhito Totani, Masaki Ri, Chie Kato, Takahiro Nakashima, Nana Suzuki, Shinya Hagiwara, Takashi Kanamori, Satsuki Murakami, Arisa Masuda, Shiori Kinoshita, Takashi Yoshida, Tomoko Narita, Asahi Ito, Shigeru Kusumoto, Takashi Ishida, Hirokazu Komatsu, Shinsuke Iida, INTERNATIONAL JOURNAL OF HEMATOLOGY, 103, (3) 316 - 321,   2016年03月, 査読有り, Proteasome inhibitors (PIs) in combination with immunomodulatory drugs (IMiDs) have been shown to be effective against relapsed/refractory multiple myeloma (RRMM). To determine the optimal dosing schedule of once weekly bortezomib (BTZ) combined with lenalidomide (LEN) and dexamethasone (DEX), especially in the outpatient setting, we conducted a phase I dose escalation study. A 21-day cycle of BTZ 1.3 mg/m(2) on days 1 and 8, LEN 10 mg/day (cohort 1) or 15 mg/day (cohort 2) on days 1-14, and DEX 20 mg/day on days 1, 2, 8, and 9 was administered. Three patients were enrolled in each cohort. No dose-limiting toxicity was observed in either cohort. Although hematological toxicities estimated as > grade 3 were common, non-hematological toxicities of grade 3 or higher were rare. Two cases of newly diagnosed peripheral neuropathy (PN) were observed, while no grade 3/4 PN was observed. Two patients achieved partial response and two achieved stable disease. The recommended doses of BTZ and LEN were determined to be 1.3 mg/m(2) and 15 mg, respectively. Combination therapy of once weekly BTZ with LEN and DEX was well tolerated and shows promise as a regimen for patients with RRMM previously treated with both PIs and IMiDs.
  • Labial salivary gland biopsy for diagnosing immunoglobulin light chain amyloidosis: a retrospective analysis, Tomotaka Suzuki, Shigeru Kusumoto, Taro Yamashita, Arisa Masuda, Shiori Kinoshita, Takashi Yoshida, Fumiko Takami-Mori, Hisashi Takino, Asahi Ito, Masaki Ri, Takashi Ishida, Hirokazu Komatsu, Mitsuharu Ueda, Yukio Ando, Hiroshi Inagaki, Shinsuke Iida, ANNALS OF HEMATOLOGY, 95, (2) 279 - 285,   2016年01月, 査読有り, Our goal was to evaluate the usefulness of labial salivary gland (LSG) biopsy for diagnosing immunoglobulin light chain (AL) amyloidosis, by comparing bone marrow and skin biopsies in the same patient population. This retrospective study included 34 consecutive patients who showed evidence of monoclonal proteins and symptoms considered to be due to amyloidosis, and who underwent a tissue biopsy from LSG between January 2005 and December 2012 at Nagoya City University Hospital. All samples of superficial tissues, including LSG, bone marrow, and skin, were independently evaluated as having amyloid deposits by a central review, which was blind to clinical information. An AL amyloidosis diagnosis was based on evidence of amyloid deposition in any biopsied tissue. Eighteen patients were diagnosed with AL amyloidosis. The sensitivity for detecting amyloid deposition was highest in biopsies of LSG at 89 %, followed by 77 % for bone marrow, and 72 % for skin. Amyloid deposition was detected in at least one superficial tissue of all the 18 patients. An LSG biopsy may be appropriate as a first-choice procedure to diagnose AL amyloidosis. Multiple biopsies of superficial tissues, including LSG, bone marrow, and skin, are recommended to increase the sensitivity for diagnosing AL amyloidosis.
  • Long-term follow-up results of a phase I/II study of melphalan, prednisolone and bortezomib in Japanese transplant-ineligible multiple myeloma patients (JPN-102)., Ogiya D, Shibayama H, Nakatani E, Ando K, Suzuki K, Kuroda Y, Uchida T, Maruyama D, Matsumoto M, Matsue K, Iida S, Terui Y, Ri M, Chou T, Aotsuka N, Tabata S, Konishi J, Ohashi K, Shinagawa A, Sugiura I, Kuroda J, Miyamoto T, Ogura M, Tobinai K, Kanakura Y, Hotta T, [Rinsho ketsueki] The Japanese journal of clinical hematology, 57, (11) 2311 - 2318,   2016年, 査読有り
  • Overexpression of salivary-type amylase reduces the sensitivity to bortezomib in multiple myeloma cells., Mizuno S, Hanamura I, Ota A, Karnan S, Narita T, Ri M, Mizutani M, Goto M, Gotou M, Tsunekawa N, Shikami M, Iida S, Hosokawa Y, Miwa H, Ueda R, Nitta M, Takami A, International journal of hematology, 102, (5) 569 - 578,   2015年11月, 査読有り
  • [Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma]., Masaki A, Ishida T, Maeda Y, Suzuki S, Ito A, Takino H, Totani H, Yoshida T, Kinoshita S, Ogura H, Narita T, Ri M, Kusumoto S, Inagaki A, Komatsu H, Niimi A, Ueda R, Utsunomiya A, Inagaki H, Iida S, [Rinsho ketsueki] The Japanese journal of clinical hematology, 56, (11) 2295 - 2304,   2015年11月, 査読有り
  • Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma., Masaki A, Ishida T, Maeda Y, Suzuki S, Ito A, Takino H, Ogura H, Totani H, Yoshida T, Kinoshita S, Narita T, Ri M, Kusumoto S, Inagaki A, Komatsu H, Niimi A, Ueda R, Utsunomiya A, Inagaki H, Iida S, Clinical cancer research : an official journal of the American Association for Cancer Research, 21, (12) 2830 - 2839,   2015年06月, 査読有り
  • [Transplant-Related Mortality Following Allogeneic Hematopoietic Stem Cell Transplantation Using Fludarabine/Busulfan-Based Reduced-Intensity Conditioning - A Retrospective Analysis in a Single Institution]., Yoshida T, Kusumoto S, Masuda A, Totani H, Narita T, Masaki A, Ito A, Ri M, Ishida T, Komatsu H, Iida S, Gan to kagaku ryoho. Cancer & chemotherapy, 42, (6) 719 - 724,   2015年06月, 査読有り
  • TM-233, a novel analog of 1'-acetoxychavicol acetate, induces cell death in myeloma cells by inhibiting both JAK/STAT and proteasome activities., Sagawa M, Tabayashi T, Kimura Y, Tomikawa T, Nemoto-Anan T, Watanabe R, Tokuhira M, Ri M, Hashimoto Y, Iida S, Kizaki M, Cancer science, 106, (4) 438 - 446,   2015年04月, 査読有り
  • Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy., Totani H, Kusumoto S, Ishida T, Masuda A, Yoshida T, Ito A, Ri M, Komatsu H, Murakami S, Mizokami M, Ueda R, Niimi A, Inagaki H, Tanaka Y, Iida S, International journal of hematology, 101, (4) 398 - 404,   2015年04月, 査読有り
  • Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells., Wada N, Kawano Y, Fujiwara S, Kikukawa Y, Okuno Y, Tasaki M, Ueda M, Ando Y, Yoshinaga K, Ri M, Iida S, Nakashima T, Shiotsu Y, Mitsuya H, Hata H, International journal of oncology, 46, (3) 963 - 972,   2015年03月, 査読有り
  • Lipopolysaccharide-Induced CXCL10 mRNA Level and Six Stimulant-mRNA Combinations in Whole Blood: Novel Biomarkers for Bortezomib Responses Obtained from a Prospective Multicenter Trial for Patients with Multiple Myeloma., Watanabe T, Mitsuhashi M, Sagawa M, Ri M, Suzuki K, Abe M, Ohmachi K, Nakagawa Y, Nakamura S, Chosa M, Iida S, Kizaki M, PloS one, 10, (6) ,   2015年, 査読有り
  • Phosphoinositide Protein Kinase PDPK1 Is a Crucial Cell Signaling Mediator in Multiple Myeloma, Yoshiaki Chinen, Junya Kuroda, Yuji Shimura, Hisao Nagoshi, Miki Kiyota, Mio Yamamoto-Sugitani, Shinsuke Mizutani, Natsumi Sakamoto, Masaki Ri, Eri Kawata, Tsutomu Kobayashi, Yosuke Matsumoto, Shigeo Horiike, Shinsuke Iida, Masafumi Taniwaki, CANCER RESEARCH, 74, (24) 7418 - 7429,   2014年12月, 査読有り, Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. (C)2014 AACR.
  • Prognostic impact of microRNA-145 down-regulation in adult T-cell leukemia/lymphoma, Hongjing Xia, Seiji Yamada, Mineyoshi Aoyama, Fumihiko Sato, Ayako Masaki, Yan Ge, Masaki Ri, Takashi Ishida, Ryuzo Ueda, Atae Utsunomiya, Kiyofumi Asai, Hiroshi Inagaki, HUMAN PATHOLOGY, 45, (6) 1192 - 1198,   2014年06月, 査読有り, Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive tumor caused by human T-cell leukemia virus type 1. MicroRNAs (miRNAs) are closely involved in the development and progression of various tumors. Here we investigated the dysregulation of miRNAs in ATL and its clinical significance. Studies using miRNA arrays and subsequent real-time reverse transcription polymerase chain reaction showed that, in the 9 ATL cell lines examined, 1 miRNA was consistently up-regulated, whereas another 3 were consistently down-regulated, compared with normal CD4-positive lymphocytes. Next, we analyzed the prognostic impact of these 4 miRNAs in patients with aggressive-type AIL (n = 40). Of the 4 dysregulated miRNAs selected, 3 (miR-130b higher expression, miR-145 lower expression, and miR-223 lower expression) were significantly associated with a worsened overall patient survival. We found that expressions of these 3 miRNAs were correlated with each other. To clarify which of the 3 had the most significant impact on overall survival, we performed a multivariate prognostic analysis that included these 3 miRNAs, and only miR-145 lower expression was selected as an independent risk factor (P = .0005). When overexpressed in an AIL cell line in vitro, miR-145 specifically inhibited tumor cell growth. In conclusion, our study suggests that miR-145 down-regulation provides a growth advantage in ATL and is highly associated with a worsened prognosis for patients with ALT. Hence, miR-145 may be a useful prognostic marker and a potential therapeutic target for ATL. (C) 2014 Elsevier Inc. All rights reserved.
  • Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model, Fumiko Mori, Takashi Ishida, Asahi Ito, Fumihiko Sato, Ayako Masaki, Tomoko Narita, Susumu Suzuki, Tomiko Yamada, Hisashi Takino, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Masakatsu Hishizawa, Kazunori Imada, Akifumi Takaori-Kondo, Akio Niimi, Ryuzo Ueda, Hiroshi Inagaki, Shinsuke Iida, EUROPEAN JOURNAL OF HAEMATOLOGY, 92, (3) 219 - 228,   2014年03月, 査読有り, ObjectiveThe objective of this study was to evaluate the therapeutic potential of bevacizumab with or without systemic chemotherapy for adult T-cell leukemia/lymphoma (ATL) and clarify the significance of angiogenesis for ATL pathogenesis. MethodsNOD/Shi-scid, IL-2R(null) (NOG) mice were used as recipients of tumor cells from a patient with ATL, which engraft and proliferate in a microenvironment-dependent manner. The ATL cells could be serially transplanted in NOG mice, but could not be maintained in in vitro cultures. ResultsInjection of bevacizumab alone significantly increased necrosis and decreased vascularization in the tumor tissue. Levels of human soluble interleukin two receptor in the serum (reflecting the ATL tumor burden) of bevacizumab-treated mice were significantly lower than in untreated mice. Although bevacizumab monotherapy showed these clear anti-angiogenesis effects, it did not prolong survival. In contrast, injection of bevacizumab together with cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) led to a significant prolongation of survival of the ATL mice relative to CHOP alone. ConclusionsThis is the first report to evaluate the efficacy of bevacizumab for ATL in a tumor microenvironment-dependent model. Bevacizumab therapy combined with chemotherapy could be a valuable treatment strategy for that subgroup of ATL probably depending to a large extent on angiogenesis via vascular endothelial growth factor.
  • Design, synthesis, and biological activity of NCC149 derivatives as histone deacetylasea 8-selective inhibitors, Takayoshi Suzuki, Nobusuke Muto, Masashige Bando, Yukihiro Itoh, Ayako Masaki, Masaki Ri, Yosuke Ota, Hidehiko Nakagawa, Shinsuke Iida, Katsuhiko Shirahige, Naoki Miyata, ChemMedChem, 9, (3) 657 - 664,   2014年03月, 査読有り, We recently discovered N-hydroxy-3-[1-(phenylthio)methyl-1H-1,2,3-triazol- 4-yl]benzamide (NCC149) as a potent and selective histone deacetylasea 8 (HDAC8) inhibitor from a 151-member triazole compound library using a click chemistry approach. In this work, we present a series of NCC149 derivatives bearing various aromatic linkers that were designed and synthesized as HDAC8-selective inhibitors. A series of in vitro assays were used to evaluate the newly synthesized compounds, four of which showed HDAC8 inhibitory activity similar to that of NCC149, and one of which displayed HDAC8 selectivity superior to that of NCC149. In addition, these top four compounds induced the increase of acetylated cohesin (an HDAC8 substrate) in HeLa cells in a dose-dependent manner, indicating inhibition of HDAC8 in the cells. While none of these compounds enhanced the acetylation of H3K9 (a substrate of HDAC1 and 2), only one compound refrained from increasing α-tubulin acetylation, a substrate of HDAC6, indicating that this compound is more selective for HDAC8 than the other derivatives. Furthermore, this HDAC8-selective inhibitor suppressed the growth of T-cell lymphoma cells more potently than did NCC149. These findings are useful for the further development of HDAC8-selective inhibitors. © 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.
  • [Determinants of sensitivity to proteasome inhibitors and strategies to overcome acquired resistance to bortezomib in multiple myeloma]., Iida S, Ri M, [Rinsho ketsueki] The Japanese journal of clinical hematology, 55, (3) 304 - 310,   2014年03月, 査読有り
  • HTLV-1 bZIP Factor-Specific CD4 T Cell Responses in Adult T Cell Leukemia/Lymphoma Patients after Allogeneic Hematopoietic Stem Cell Transplantation, Tomoko Narita, Takashi Ishida, Ayako Masaki, Susumu Suzuki, Asahi Ito, Fumiko Mori, Tomiko Yamada, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Yasuhiko Miyazaki, Yoshifusa Takatsuka, Atae Utsunomiya, Akio Niimi, Shinsuke Iida, Ryuzo Ueda, JOURNAL OF IMMUNOLOGY, 192, (3) 940 - 947,   2014年02月, 査読有り, We document human T lymphotropic virus type 1 (HTLV-1) bZIP factor (HBZ)-specific CD4 T cell responses in an adult T cell leukemia/lymphoma (ATL) patient after allogeneic hematopoietic stem cell transplantation (HCT) and identified a novel HLA-DRB1* 15:01-restricted HBZ-derived naturally presented minimum epitope sequence, RRRAEKKAADVA (HBZ114-125). This peptide was also presented on HLA-DRB1*15:02, recognized by CD4 T cells. Notably, HBZ-specific CD4 T cell responses were only observed in ATL patients after allogeneic HCT (4 of 9 patients) and not in nontransplanted ATL patients (0 of 10 patients) or in asymptomatic HTLV-1 carriers (0 of 10 carriers). In addition, in one acute-type patient, HBZ-specific CD4 T cell responses were absent in complete remission before HCT, but they became detectable after allogeneic HCT. We surmise that HTLV-1 transmission from mothers to infants through breast milk in early life induces tolerance to HBZ and results in insufficient HBZ-specific T cell responses in HTLV-1 asymptomatic carriers or ATL patients. In contrast, after allogeneic HCT, the reconstituted immune system from donor-derived cells can recognize virus protein HBZ as foreign, and HBZ-specific immune responses are provoked that contribute to the graft-versus-HTLV-1 effect.
  • Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma, Atsushi Inagaki, Emi Tajima, Miyuki Uranishi, Haruhito Totani, Yu Asao, Hiroka Ogura, Ayako Masaki, Tatsuya Yoshida, Fumiko Mori, Asahi Ito, Hiroki Yano, Masaki Ri, Satoshi Kayukawa, Takae Kataoka, Shigeru Kusumoto, Takashi Ishida, Yoshihito Hayami, Ichiro Hanamura, Hirokazu Komatsu, Hiroshi Inagaki, Yasufumi Matsuda, Ryuzo Ueda, Shinsuke Iida, LEUKEMIA RESEARCH, 37, (12) 1648 - 1655,   2013年12月, 査読有り, CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQJRT-PCR. CCNDI, FGFR3 and c-MAF were positive in 44(36%), 28(23%) and 16(13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF-positive patients. Thus, CCNDI, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients. (C) 2013 Elsevier Ltd. All rights reserved.
  • [Myeloma therapy (3) Trends in development of new drugs]., Ri M, Iida S, [Rinsho ketsueki] The Japanese journal of clinical hematology, 54, (8) 715 - 718,   2013年08月, 査読有り
  • Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model., Masaki A, Ishida T, Suzuki S, Ito A, Mori F, Sato F, Narita T, Yamada T, Ri M, Kusumoto S, Komatsu H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R, Journal of immunology (Baltimore, Md. : 1950), 191, (1) 135 - 144,   2013年07月, 査読有り
  • Successful salvage therapy using lenalidomide in a patient with relapsed multiple myeloma after allogeneic hematopoietic stem cell transplantation, Tomotaka Suzuki, Shigeru Kusumoto, Tatsuya Yoshida, Fumiko Mori, Asahi Ito, Masaki Ri, Takashi Ishida, Hirokazu Komatsu, Akio Niimi, Shinsuke Iida, INTERNATIONAL JOURNAL OF HEMATOLOGY, 97, (4) 540 - 543,   2013年04月, 査読有り
  • Angioimmunoblastic T-cell lymphoma mice model, Fumihiko Sato, Takashi Ishida, Asahi Ito, Fumiko Mori, Ayako Masaki, Hisashi Takino, Tomoko Narita, Masaki Ri, Shigeru Kusumoto, Susumu Suzuki, Hirokazu Komatsu, Akio Niimi, Ryuzo Ueda, Hiroshi Inagaki, Shinsuke Iida, LEUKEMIA RESEARCH, 37, (1) 21 - 27,   2013年01月, 査読有り, We established an angioimmunoblastic T-cell lymphoma (AITL) mouse model using NOD/Shi-scid, IL-2R gamma(null) mice as recipients. The immunohistological findings of the AITL mice were almost identical to those of patients with AITL. In addition, substantial amounts of human immunoglobulin G/A/M were detected in the sera of the AITL mice. This result indicates that AITL tumor cells helped antibody production by B cells or plasma cells. This is the first report of reconstituting follicular helper T (TFH) function in AITL cells in an experimental model, and this is consistent with the theory that TFH cell is the cell of origin of AITL tumor cells. (C) 2012 Elsevier Ltd. All rights reserved.
  • RSK2(Ser227) at N-Terminal Kinase Domain Is a Potential Therapeutic Target for Multiple Myeloma, Yuji Shimura, Junya Kuroda, Masaki Ri, Hisao Nagoshi, Mio Yamamoto-Sugitani, Tsutomu Kobayashi, Miki Kiyota, Ryuko Nakayama, Shinsuke Mizutani, Yoshiaki Chinen, Natsumi Sakamoto, Yosuke Matsumoto, Shigeo Horiike, Yukimasa Shiotsu, Shinsuke Iida, Masafumi Taniwaki, MOLECULAR CANCER THERAPEUTICS, 11, (12) 2600 - 2609,   2012年12月, 査読有り, Multiple myeloma is an entity of cytogenetically and genetically heterogenous plasma cell neoplasms. Despite recent improvement in the treatment outcome of multiple myeloma by novel molecular-targeted chemotherapeutics, multiple myeloma remains incurable. The identification of a therapeutic target molecule in which various signaling for cell-survival converge is a core component for the development of new therapeutic strategies against multiple myeloma. RSK2 is an essential mediator of the ERK1/2 signaling pathway for cell survival and proliferation. In this study, we discovered that RSK2(Ser227), which is located at the N-terminal kinase domain and is one site responsible for substrate phosphorylation, is activated through phosphorylation regardless of the type of cytogenetic abnormalities or upstream molecular signaling in all 12 multiple myeloma-derived cell lines examined and 6 of 9 patient-derived CD138-positive primary myeloma cells. The chemical inhibition of RSK2(Ser227) by BI-D1870 or gene knockdown of RSK2 inhibits myeloma cell proliferation through apoptosis induction, and this anti-myeloma effect was accompanied by downregulation of c-MYC, cyclin D, p21(WAF1/CIP1), and MCL1. RSK2(Ser227) inhibition resulting from BI-D1870 treatment restored lenalidomide-induced direct cytotoxicity of myeloma cells from interleukin-6-mediated cell protection, showed no cross-resistance to bortezomib, and exerted additive/synergistic antiproliferative effects in conjunction with the mTOR, histone deacetylase, and BH3-mimicking BCL2/BCLXL inhibitors. These results suggest that RSK2(Ser227) is a potential therapeutic target not only for newly diagnosed but also for patients with later phase multiple myeloma who are resistant or refractory to currently available anti-myeloma therapies. Mol Cancer Ther; 11(12); 2600-9. (C)2012 AACR.
  • Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries, Takayoshi Suzuki, Yosuke Ota, Masaki Ri, Masashige Bando, Aogu Gotoh, Yukihiro Itoh, Hiroki Tsumoto, Prima R. Tatum, Tamio Mizukami, Hidehiko Nakagawa, Shinsuke Iida, Ryuzo Ueda, Katsuhiko Shirahige, Naoki Miyata, Journal of Medicinal Chemistry, 55, (22) 9562 - 9575,   2012年11月26日, 査読有り, To find HDAC8-selective inhibitors, we designed a library of HDAC inhibitor candidates, each containing a zinc-binding group that coordinates with the active-site zinc ion, linked via a triazole moiety to a capping structure that interacts with residues on the rim of the active site. These compounds were synthesized by using click chemistry. Screening identified HDAC8-selective inhibitors including C149 (IC50 = 0.070 μM), which was more potent than PCI-34058 (6) (IC50 = 0.31 μM), a known HDAC8 inhibitor. Molecular modeling suggested that the phenylthiomethyl group of C149 binds to a unique hydrophobic pocket of HDAC8, and the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the triazole moiety) is important for the potency and selectivity. The inhibitors caused selective acetylation of cohesin in cells and exerted growth-inhibitory effects on T-cell lymphoma and neuroblastoma cells (GI50 = 3-80 μM). These findings suggest that HDAC8-selective inhibitors have potential as anticancer agents. © 2012 American Chemical Society.
  • Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma., Suzuki S, Masaki A, Ishida T, Ito A, Mori F, Sato F, Narita T, Ri M, Kusumoto S, Komatsu H, Fukumori Y, Nishikawa H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R, Cancer science, 103, (10) 1764 - 1773,   2012年10月, 査読有り
  • Forkhead box P1 overexpression and its clinicopathologic significance in peripheral T-cell lymphoma, not otherwise specified, Seiji Yamada, Fumihiko Sato, Hongjing Xia, Hisashi Takino, Satoru Kominato, Masaki Ri, Takashi Ishida, Shinsuke Iida, Hiroshi Inagaki, Kazuo Yamada, HUMAN PATHOLOGY, 43, (8) 1322 - 1327,   2012年08月, 査読有り, Forkhead box P1 protein is a transcription factor involved in cell signaling and regulation of gene expression and is essential for B-cell development. Forkhead box P1 overexpression has been associated with a worsened prognosis in some B-cell lymphomas. However, little is known about the clinicopathologic significance of forkhead box P1 in T-cell malignancies. In this study, immunohistochemistry for forkhead box P1 was performed in peripheral T-cell lymphoma, not otherwise specified, cases (n = 41), which were then divided into lower (n = 15) and higher (n = 26) forkhead box P1 expressers. Results of real-time quantitative reverse transcriptase polymerase chain reaction for forkhead box P1 messenger RNA supported the data on immunohistochemical forkhead box P1 expression. Forkhead box P1 overexpression in lymphoma cells was inversely associated with proliferation activity as evaluated by Ki-67 expression. Double immunostain for forkhead box P1 and a T-cell marker in normal lymph nodes showed forkhead box P1 signals in many of nonneoplastic T cells. Prognostic analysis showed that forkhead box P1 overexpression was associated with an improved overall survival of the patients with peripheral T-cell lymphoma, not otherwise specified, and was independent of the International Prognostic Index in multivariate analysis. Forkhead box P1 overexpression may be associated with less activated phenotype of the tumors and with a better prognosis in patients with peripheral T-cell lymphoma, not otherwise specified. The clinicopathologic significance of forkhead box P1 overexpression in peripheral T-cell lymphoma, not otherwise specified, may be different from that in B-cell lymphomas. (C) 2012 Elsevier Inc. All rights reserved.
  • A complement-dependent cytotoxicity-enhancing anti-CD20 antibody mediating potent antitumor activity in the humanized NOD/Shi-scid, IL-2Rγ(null) mouse lymphoma model., Sato F, Ito A, Ishida T, Mori F, Takino H, Inagaki A, Ri M, Kusumoto S, Komatsu H, Iida S, Okada N, Inagaki H, Ueda R, Cancer immunology, immunotherapy : CII, 59, (12) 1791 - 1800,   2010年12月, 査読有り
  • Reactivation of hepatitis B virus in HBsAg-negative patients with multiple myeloma: two case reports, Tatsuya Yoshida, Shigeru Kusumoto, Atsushi Inagaki, Fumiko Mori, Asahi Ito, Masaki Ri, Takashi Ishida, Hirokazu Komatsu, Shinsuke Iida, Fuminaka Sugauchi, Yasuhito Tanaka, Masashi Mizokami, Ryuzo Ueda, INTERNATIONAL JOURNAL OF HEMATOLOGY, 91, (5) 844 - 849,   2010年06月, 査読有り, It was recently reported that hepatitis B virus (HBV) reactivation had occurred in HBsAg-negative lymphoma patients who received rituximab plus steroid combination chemotherapy. HBV reactivation in myeloma patients have not been reported extensively. We describe here two cases of HBV reactivation in HBsAg-negative myeloma patients receiving systemic chemotherapy: one from the medical records of 40 patients and another from 61 patients with prospective HBV-DNA monitoring. In the first case positive for anti-HBs, HBV reactivation was diagnosed when hepatitis developed during conventional chemotherapy such as MP and MCP regimen in a relapsed patient after autologous stem cell transplantation (APBSCT); in the second case positive for anti-HBc and anti-HBs, elevation of HBV-DNA was recognized by serial HBV-DNA monitoring performed prospectively following APBSCT. Interestingly, these two cases had the reduction of the titer of anti-HBs during the treatment, followed by HBV reactivation. These clinical data suggest that the HBV-DNA monitoring is necessary for not only HBsAg-positive but also HBsAg-negative myeloma patients with anti-HBc-positive and/or anti-HBs-positive following transplantation and after conventional chemotherapy in the salvage setting. Establishment of a standard strategy to prevent HBV reactivation is important for myeloma patients receiving systemic chemotherapy.
  • [Anti-CCR4 monoclonal antibody as a novel therapy for advanced mycosis fungoides and Sézary syndrome]., Yano H, Ishida T, Inagaki A, Ishii T, Ri M, Ito A, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R, [Rinsho ketsueki] The Japanese journal of clinical hematology, 50, (12) 1671 - 1678,   2009年12月, 査読有り
  • The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity., Ding J, Komatsu H, Iida S, Yano H, Kusumoto S, Inagaki A, Mori F, Ri M, Ito A, Wakita A, Ishida T, Nitta M, Ueda R, Blood, 114, (15) 3325 - 3328,   2009年10月, 査読有り
  • Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary ATLL cells mediated by autologous human immune cells in NOD/Shi-scid, IL-2R gamma(null) mice in vivo., Ito A, Ishida T, Utsunomiya A, Sato F, Mori F, Yano H, Inagaki A, Suzuki S, Takino H, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R, Journal of immunology (Baltimore, Md. : 1950), 183, (7) 4782 - 4791,   2009年10月, 査読有り
  • Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in the novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model., Ito A, Ishida T, Yano H, Inagaki A, Suzuki S, Sato F, Takino H, Mori F, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R, Cancer immunology, immunotherapy : CII, 58, (8) 1195 - 1206,   2009年08月, 査読有り
  • Expression of the ULBP ligands for NKG2D by B-NHL cells plays an important role in determining their susceptibility to rituximab-induced ADCC., Inagaki A, Ishida T, Yano H, Ishii T, Kusumoto S, Ito A, Ri M, Mori F, Ding J, Komatsu H, Iida S, Ueda R, International journal of cancer, 125, (1) 212 - 221,   2009年07月, 査読有り
  • Bortezomib-induced apoptosis in mature T-cell lymphoma cells partially depends on upregulation of Noxa and functional repression of Mcl-1., Ri M, Iida S, Ishida T, Ito A, Yano H, Inagaki A, Ding J, Kusumoto S, Komatsu H, Utsunomiya A, Ueda R, Cancer science, 100, (2) 341 - 348,   2009年02月, 査読有り
  • Overexpression of carboxylesterase-2 results in enhanced efficacy of topoisomerase I inhibitor, irinotecan (CPT-11), for multiple myeloma., Yano H, Kayukawa S, Iida S, Nakagawa C, Oguri T, Sanda T, Ding J, Mori F, Ito A, Ri M, Inagaki A, Kusumoto S, Ishida T, Komatsu H, Inagaki H, Suzuki A, Ueda R, Cancer science, 99, (11) 2309 - 2314,   2008年11月, 査読有り
  • [Histopathological findings of pulmonary complications in 16 patients who received allogeneic hematopoietic stem cell transplants]., Iida H, Ri M, Niimi K, Harada T, Sao H, [Rinsho ketsueki] The Japanese journal of clinical hematology, 46, (12) 1273 - 1278,   2005年12月, 査読有り


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