Researcher Database

Tomoyuki Endo
Hokkaido University Hospital Internal Medicine
Lecturer

Researcher Profile and Settings

Affiliation

  • Hokkaido University Hospital Internal Medicine

Job Title

  • Lecturer

J-Global ID

Research Activities

Published Papers

  • Minoru Kanaya, Tomoyuki Endo, Daigo Hashimoto, Shogo Endo, Ryo Takemura, Kohei Okada, Kanako C. Hatanaka, Yoshihiro Matsuno, Takanori Teshima
    INTERNATIONAL JOURNAL OF HEMATOLOGY 106 (2) 147 - 148 0925-5710 2017/08 [Refereed][Not invited]
  • Takahiro Tateno, Masahiro Onozawa, Junichi Hashiguchi, Takashi Ishio, Sayaka Yuzawa, Satomi Matsuoka, Mizuha Kosugi-Kanaya, Kohei Okada, Souichi Shiratori, Hideki Goto, Taichi Kimura, Junichi Sugita, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Shinya Tanaka, Satoshi Hashino, Takanori Teshima
    TRANSPLANT INFECTIOUS DISEASE 19 (4) 1398-2273 2017/08 [Refereed][Not invited]
     
    We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post-mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.
  • Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Yasushi Onishi, Tomoyuki Endo, Seitaro Terakura, Yuichi Ishikawa, Chisako Iriyama, Yoko Ushijima, Tatsunori Goto, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Noriko Fukuhara, Yoshihiro Inamoto, Ritsuro Suzuki, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida
    Cancer science 108 (8) 1634 - 1639 1347-9032 2017/08 [Refereed][Not invited]
     
    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.
  • Naohiro Miyashita, Tomoyuki Endo, Masahiro Onozawa, Daigo Hashimoto, Takeshi Kondo, Katsuya Fujimoto, Kaoru Kahata, Junichi Sugita, Hideki Goto, Toshihiro Matsukawa, Satoshi Hashino, Takanori Teshima
    TRANSPLANT INFECTIOUS DISEASE 19 (3) 1398-2273 2017/06 [Refereed][Not invited]
     
    Background: Human herpesvirus 6 (HHV-6) encephalitis/myelitis is now a well-known complication after allogeneic stem cell transplantation (allo-HSCT), particularly after cord blood transplantation (CBT). In this study, we evaluated the risk factors of HHV-6 encephalitis/myelitis. Methods: We evaluated 253 patients who received allo-HSCT from 2007 to 2015 at our institute. HHV-6 encephalitis/myelitis was defined as HHV-6 DNA detection in the cerebrospinal fluid or peripheral blood by polymerase chain reaction in the presence of typical manifestations without other concurrent condition that led to the manifestations. Results: HHV-6 encephalitis/myelitis occurred in 11 patients (4.5%) (9 encephalitis, 3.7%; 2 myelitis, 0.8%). Multivariate analysis showed that CBT, mycophenolate mofetil (MMF) for graft-versus-host disease prophylaxis, history of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and engraftment syndrome (ES) were significantly associated with incidence of HHV-6 encephalitis/myelitis (P=.025, P=.017, P=.017, and P=.014, respectively). Conclusion: Although it has been shown that CBT, ES, and history of allo-HSCT are risk factors for HHV-6 encephalitis/myelitis, our study demonstrated MMF is also a risk factor for the disease.
  • Toshihiro Matsukawa, Daigo Hashimoto, Junichi Sugita, Seitarou Nakazawa, Takae Matsushita, Haruhiko Kashiwazaki, Hideki Goto, Masahiro Onozawa, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Yutaka Yamazaki, Takanori Teshima
    INTERNATIONAL JOURNAL OF HEMATOLOGY 104 (1) 117 - 124 0925-5710 2016/07 [Refereed][Not invited]
     
    Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT. Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m(2); days +3 and +6: 10 mg/m(2)) with 10-7-7 MTX (day +1: 10 mg/m(2); day +3 and +6: 7 mg/m(2)) in combination with tacrolimus. The cumulative incidence rates of grades II-IV acute GVHD, grades III-IV acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent. The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11-31 days), while that in the 10-7-7 group was 15 days (range, 12-19 days) (P = 0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13-49 days) than that in the 15-10-10 MTX group (27 days; range, 9-405 days) (P = 0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P = 0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD.
  • Souichi Shiratori, Katsuya Fujimoto, Machiko Nishimura, Kanako C. Hatanaka, Mizuha Kosugi-Kanaya, Kohei Okada, Junichi Sugita, Akio Shigematsu, Daigo Hashimoto, Tomoyuki Endo, Takeshi Kondo, Riichiro Abe, Satoshi Hashino, Yoshihiro Matsuno, Hiroshi Shimizu, Takanori Teshima
    HEMATOLOGICAL ONCOLOGY 34 (1) 9 - 16 0278-0232 2016/03 [Refereed][Not invited]
     
    Advanced-stage mycosis fungoides and Sezary syndrome (MF/SS) have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT), particularly using a reduced-intensity conditioning (RIC) regimen, is a promising treatment for advanced-stage MF/SS. We performed RIC-HSCT in nine patients with advanced MF/SS. With a median follow-up period of 954days after HSCT, the estimated 3-year overall survival was 85.7% (95% confidence interval, 33.4-97.9%) with no non-relapse mortality. Five patients relapsed after RIC-HSCT; however, in four patients whose relapse was detected only from the skin, persistent complete response was achieved in one patient, and the disease was manageable in other three patients by the tapering of immunosuppressants and donor lymphocyte infusion, suggesting that graft-versus-lymphoma effect and down-staging' effect from advanced stage to early stage by HSCT improve the prognosis of advanced-stage MF/SS. These results suggest that RIC-HSCT is an effective treatment for advanced MF/SS. Copyright (c) 2014 John Wiley & Sons, Ltd.
  • Kasahara K, Onozawa M, Miyashita N, Yokohata E, Yoshida M, Kanaya M, Kosugi-Kanaya M, Takemura R, Takahashi S, Sugita J, Shigematsu A, Takahata M, Fujisawa S, Hashimoto D, Fujimoto K, Endo T, Kondo T, Teshima T
    Case reports in hematology 2016 2373902  2090-6560 2016 [Refereed][Not invited]
  • Yuki Tazawa, Akio Shigematsu, Kumiko Kasashi, Junichi Sugita, Tomoyuki Endo, Takeshi Kondo, Takanori Teshima, Ken Iseki, Mitsuru Sugawara, Yoh Takekuma
    Journal of pharmaceutical health care and sciences 2 18 - 18 2016 [Refereed][Not invited]
     
    BACKGROUND: We investigated the pharmacokinetics of etoposide (ETP) to reduce the inter-individual variations of ETP concentrations in patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation. We also carried out an in vivo study using rats to verify the dose adjustment. METHODS: This study included 20 adult patients. ETP was administered intravenously at a dose of 15 mg/kg once daily for 2 days (total dose: 30 mg/kg) combined with standard conditioning of cyclophosphamide and total body irradiation. In an in vivo study using rats, ETP was administered intravenously at a dose of 15 mg/kg or an adjusted dose. The ETP plasma concentration was determined by using HPLC. The pharmacokinetic parameters were estimated by using a 1-compartment model. RESULTS: The peak concentration (Cmax) of ETP and the area under the plasma concentration-time curve (AUC) of ETP differed greatly among patients (range of Cmax, 51.8 - 116.5 μg/mL; range of AUC, 870 - 2015 μg · h/mL). A significant relationship was found between Cmax and AUC (R = 0.85, P < 0.05). Distribution volume (Vd) was suggested to be one of the factors of inter-individual variation in plasma concentration of ETP in patients (range of Vd, 0.13 - 0.27 L/kg), and correlated with Alb and body weight (R = 0.56, P < 0.05; R = 0.40, P < 0.05 respectively). We predicted Vd of rats by body weight of rats (with normal albumin levels and renal function), and the dose of ETP was adjusted using predicted Vd. In the dose adjustment group, the target plasma ETP concentration was achieved and the variation of plasma ETP concentration was decreased. CONCLUSION: The results suggested that inter-individual variation of plasma concentration of ETP could be reduced by predicting Vd. Prediction of Vd is effective for reducing individual variation of ETP concentration and might enable a good therapeutic effect to be achieved.
  • Mutsumi Nishida, Akio Shigematsu, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Takahito Iwai, Tomoyuki Endo, Akihiro Iguchi, Hitoshi Shibuya, Kanako Hatanaka, Chikara Shimizu, Takanori Teshima
    CLINICAL TRANSPLANTATION 29 (8) 697 - 704 0902-0063 2015/08 [Refereed][Not invited]
     
    Gastrointestinal graft-versus-host disease (GI-GVHD) is a major and life-threatening complication of hematopoietic stem cell transplantation (HSCT). This study evaluated the efficacy of ultrasonography (US) for assessing and monitoring GI-GVHD. GI tract was evaluated by US in 81 patients. US findings were positive in 43 patients, including 11 false positive, and negative in 38 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for the diagnosis of GI-GVHD were 100%, 78%, 74%, 100%, and 86%, respectively. Diffuse wall thickening of the ileum was the most frequent finding in patients with GI-GVHD. Severity of GI-GVHD was correlated with the thickness of internal low echoic layer of the wall, the echogenicity of mesenteric fat tissue, and the intensity of Doppler signaling. We classified US findings of GI-GVHD into four USgrades. There was a significant correlation between clinical stage of GI-GVHD and the US grade. These ultrasonographic abnormalities were improved with clinical improvement of GI-GVHD upon treatment. Thus, US is an effective and efficient non-invasive means of identifying the extent and severity of GI-GVHD and monitoring response to treatment.
  • Keisuke Imafuku, Yukiko Nomura, Chihiro Nakayama, Riichiro Abe, Tomoyuki Endo, Hiroshi Shimizu
    British journal of haematology 170 (2) 140 - 140 0007-1048 2015/07 [Refereed][Not invited]
  • Leonard Christopher Schmeel, Frederic Carsten Schmeel, Young Kim, Sabine Blaum-Feder, Tomoyuki Endo, Ingo G. H. Schmidt-Wolf
    ANTICANCER RESEARCH 35 (3) 1369 - 1376 0250-7005 2015/03 [Refereed][Not invited]
     
    Background/Aim: Novel agents such as lenalidomide and bortezomib have significantly improved today's therapy of multiple myeloma. Despite recent innovations, new therapeutic options are needed. The Wingless-related integration site (WNT) pathway is aberrantly activated in lymphoma and myeloma and therefore renders WNT signaling molecules attractive for the development of targeted therapies. Flunarizine was used in this study as it has chemical features similar to those of other known WNT inhibitors and already proven proapoptotic properties in leukemia cells. Materials and Methods: The antitumor apoptotic effect of flunarizine at doses ranging from 0.1-200 mu M was investigated on three human lymphoma cell lines, one in urine and four human myeloma cell lines by 3'3-Dihexyloxacarbocyanine iodide and propidium iodide staining in flow cytometry. Results: Flunarizine induced significant apoptotic activity in all tested myeloma and lymphoma cell lines in a dose-dependent manner. Conclusion: Our results reveal a significant selective induction of apoptosis by flunarizine and suggest an in vivo effect against lymphoma and myeloma.
  • Leonard Christopher Schmeel, Frederic Carsten Schmeel, Young Kim, Sabine Blaum-Feder, Tomoyuki Endo, Ingo G. H. Schmidt-Wolf
    ANTICANCER RESEARCH 35 (2) 835 - 841 0250-7005 2015/02 [Refereed][Not invited]
     
    Background/Aim: Multiple myeloma, a well-known but still incurable disease, is a hematological malignancy of B-lymphocytes. While standard chemotherapy regimens have been used for years, novel agents, such as lenalidomide and bortezomib, have become an essential part of today's therapies. Nevertheless, new therapeutical strategies are required in the future. Aberrant activation of wingless-related integration site (WNT)/beta-catenin signaling promotes the development of several types of cancer. Recently, it has been demonstrated that the WNT pathway is also activated in lymphoma and myeloma. Thus, the WNT signaling molecules are attractive candidates for the development of targeted therapies. To this extent, we recently confirmed that the diuretic agent ethacrynic acid (EA) and the antifungal agent ciclopirox olamine (CIC) inhibit WNT signaling. Cinnarizine has similar chemical features to those of CIC. Materials and Methods: Thus, in this study the antitumor effect of cinnarizine on myeloma and lymphoma cells was investigated by DiOC6 and propidium iodide (PI)-staining in flow cytometry. Results: Cinnarizine triggered a significant apoptotic activity in all tested myeloma and lymphoma cell lines in a concentration-dependent manner. Interestingly, healthy cells were mainly unaffected. Conclusion: These results reveal a significant selective induction of apoptosis by cinnarizine that might result from an inhibition of WNT signaling and suggest an in vivo efficacy against lymphoma and myeloma.
  • Souichi Shiratori, Mizuha Kosugi-Kanaya, Akio Shigematsu, Hajime Kobayashi, Satoshi Yamamoto, Naoki Kobayashi, Hiroshi Iwasaki, Akio Mori, Yasuyuki Kunieda, Yutaka Tsutsumi, Mitsutoshi Kurosawa, Yasutaka Kakinoki, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Takanori Teshima
    LEUKEMIA & LYMPHOMA 56 (9) 2592 - 2597 1042-8194 2015 [Refereed][Not invited]
     
    Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin lymphoma and displays an aggressive clinical course with poor outcome. To identify prognostic factors for AITL, we retrospectively analyzed 36 patients with AITL. The median age was 74 years with 83% of the patients having advanced stage. Eighty-three percent received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like chemotherapies, resulting in an overall response rate of 63%. With a median follow-up of 9 years, the estimated overall survival at 5 years was 33.3%. Median serum level of soluble interleukin-2 receptor (sIL-2R) was 5615 U/mL at diagnosis, and over 10 000 U/mL of sIL-2R was identified as a significant poor prognostic factor, independent of the International Prognostic Index, Prognostic Index for peripheral T-cell lymphoma and Prognostic index for AITL (hazard ratio [HR], 4.42; 95% confidence interval [ CI], 1.49-13.11; log-rank, p < 0.01). Our study shows that an ultra-high level of serum sIL-2R at diagnosis is a significant poor prognostic biomarker for AITL.
  • Ishio T, Endo T, Okada K, Shigematsu A, Hashino S, Teshima T
    Case reports in hematology 2015 949265  2090-6560 2015 [Refereed][Not invited]
  • Toshinari Miyauchi, Riichiro Abe, Yusuke Morita, Maki Adachi, Keiko Shiba, Yohei Hamade, Nan Saito, Machiko Nishimura, Makoto Ibata, Kohei Okada, Akio Shigematsu, Tomoyuki Endo, Kazuhiro Kawai, Takanori Teshima, Hiroshi Shimizu
    ACTA DERMATO-VENEREOLOGICA 95 (8) 1024 - 1025 0001-5555 2015 [Refereed][Not invited]
  • Souichi Shiratori, Kentaro Wakasa, Kohei Okada, Junichi Sugita, Koji Akizawa, Akio Shigematsu, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Chikara Shimizu, Satoshi Hashino, Takanori Teshima
    CLINICAL TRANSPLANTATION 28 (6) 656 - 661 0902-0063 2014/06 [Refereed][Not invited]
     
    To examine risk factors for Stenotrophomonas maltophilia (S.maltophilia) infection during allogeneic hematopoietic stem cell transplantation (allo-HSCT), we retrospectively analyzed 259 patients who underwent allo-HSCT. Not only S.maltophilia infection but also S.maltophilia colonization was associated with mortality during allo-HSCT. Among 52 episodes in 39 patients in whom S.maltophilia was detected, documented infection developed in 33 episodes (25 patients). The onset of S.maltophilia infection in the period from the conditioning regimen to engraftment was associated with a high mortality rate. Breakthrough S.maltophilia infection developed in 24% of the patients during prophylactic administration of fluoroquinolones, to which S.maltophilia is sensitive. Reinsertion of a central venous catheter (CVC) immediately after removal was suggested to be a risk for persistent S.maltophilia infection in the period of neutropenia. Our results indicated that (i) onset of S.maltophilia infection in the period from the conditioning therapy to engraftment and (ii) removal and immediate reinsertion of a CVC as treatment after the onset of S.maltophilia infection are possible risk factors for S.maltophilia-related mortality during allo-HSCT.
  • Yusuke Shono, Souichi Shiratori, Mizuha Kosugi-Kanaya, Satoshi Ueha, Junichi Sugita, Akio Shigematsu, Takeshi Kondo, Daigo Hashimoto, Katsuya Fujimoto, Tomoyuki Endo, Mitsufumi Nishio, Satoshi Hashino, Yoshihiro Matsuno, Kouji Matsushima, Junji Tanaka, Masahiro Imamura, Takanori Teshima
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 20 (4) 495 - 500 1083-8791 2014/04 [Refereed][Not invited]
     
    Idiopathic cytopenias are frequently observed in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported the effect of graft-versus-host disease (GVHD) on bone marrow (BM) in murine models, indicating that the osteoblast injury mediated by donor T cells was associated with bone marrow suppression and delayed immune reconstitution. In this study, we prospectively evaluated the relevance of these findings in 51 patients. Patients with chronic GVHD manifested the loss of osteoblasts, contributing to cytopenic symptoms (P =.0427 compared with patients without cytopenic symptoms). The loss of osteoblasts was significantly associated with the extensive type of chronic GVHD (P =.012), and flow cytometric analyses revealed lower numbers of CD19(+) B cells and a significantly increased CD4 to CD8 ratio (P.0002) in these patients. Our data, for the first time to our knowledge, summarize the detailed analyses of the effect of GVHD on BM in the clinical allo-HSCT patients. (c) 2014 American Society for Blood and Marrow Transplantation.
  • Leonard Christopher Schmeel, Frederic Carsten Schmeel, Young Kim, Tomoyuki Endo, Desheng Lu, Ingo G. H. Schmidt-Wolf
    Anticancer Research 33 (11) 4719 - 4726 0250-7005 2013/11 [Refereed][Not invited]
     
    Background/Aim: Recent investigations have shown that the Wnt signaling pathway is constitutively activated in multiple myeloma (MM), thereby promoting an exaggerated cell proliferation. Thus, influencing the Wnt pathway might represent a promising target in myeloma treatment. Materials and Methods: The present study investigated whether a combination of ethacrynic acid (EA) and ciclopirox olamine (CIC) with piceatannol (PIC) would influence the Wnt pathway and viability of human and murine myeloma cell lines by using DiOC6 and propidium iodide (PI) staining, flow cytometry and immunoblotting. Results: The combination of EA with PIC as well as the combination of CIC with PIC had a significant additive effect on the vitality of myeloma cells compared to singleagent application, while healthy cells remained mainly unaffected. Additionally, EA and CIC altered the expression of β-catenin itself and its downstream factors. Conclusion: A combination of Wnt inhibitors could lead to novel treatment options for MM patients.
  • Takeshi Nishijima, Misao Takano, Michiyo Ishisaka, Hirokazu Komatsu, Hiroyuki Gatanaga, Yoshimi Kikuchi, Tomoyuki Endo, Masahide Horiba, Satoru Kaneda, Hideki Uchiumi, Tomohiko Koibuchi, Toshio Naito, Masaki Yoshida, Natsuo Tachikawa, Mikio Ueda, Yoshiyuki Yokomaku, Teruhisa Fujii, Satoshi Higasa, Kiyonori Takada, Masahiro Yamamoto, Shuzo Matsushita, Masao Tateyama, Yoshinari Tanabe, Hiroaki Mitsuya, Shinichi Oka
    Internal Medicine 52 (7) 735 - 744 0918-2918 2013 [Refereed][Not invited]
     
    Objective To compare the efficacy and safety of fixed-dose abacavir/lamivudine (ABC/3TC) and tenofovir/ emtricitabine (TDF/FTC) with ritonavir-boosted atazanavir (ATV/r) in treatment-naïve Japanese patients with HIV-1 infection. Methods A 96-week multicenter, randomized, open-label, parallel group pilot study was conducted. The endpoints were times to virologic failure, safety event and regimen modification. Results 109 patients were enrolled and randomly allocated (54 patients received ABC/3TC and 55 patients received TDF/FTC). All randomized subjects were analyzed. The time to virologic failure was not significantly different between the two arms by 96 weeks (HR, 2.09 95% CI, 0.72-6.13 p=0.178). Both regimens showed favorable viral efficacy, as in the intention-to-treat population, 72.2% (ABC/3TC) and 78.2% (TDF/ FTC) of the patients had an HIV-1 viral load < 50 copies/mL at 96 weeks. The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms (adverse event: HR 0.66 95% CI, 0.25-1.75, p=0.407) (regimen modification: HR 1.03 95% CI, 0.33- 3.19, p=0.964). Both regimens were also well-tolerated, as only 11.1% (ABC/3TC) and 10.9% (TDF/FTC) of the patients discontinued the allocated regimen by 96 weeks. Clinically suspected abacavir-associated hypersensitivity reactions occurred in only one (1.9%) patient in the ABC/3TC arm. Conclusion Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC, this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients, such as the Japanese population. © 2013 The Japanese Society of Internal Medicine.
  • Takeshi Nishijima, Hiroyuki Gatanaga, Takuro Shimbo, Hirokazu Komatsu, Tomoyuki Endo, Masahide Horiba, Michiko Koga, Toshio Naito, Ichiro Itoda, Masanori Tei, Teruhisa Fujii, Kiyonori Takada, Masahiro Yamamoto, Toshikazu Miyakawa, Yoshinari Tanabe, Hiroaki Mitsuya, Shinichi Oka
    PloS one 8 (8) e73639  2013 [Refereed][Not invited]
     
    BACKGROUND: Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral load. METHODS: This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks calculated with Cockcroft-Gault equation. RESULTS: 58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3 (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026). Per protocol analysis showed that the HIV-RNA was <50 copies/mL at week 48 in all patients of both arms (24 in RAL+DRV and 29 in LPV/r+TVD). CONCLUSIONS: Switching LPV/r+TVD to RAL+DRV/r did not significantly increase the proportion of patients who showed >10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load. TRIAL REGISTRATION: ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J).
  • Takahata M, Hashino S, Fujimoto K, Endo T, Kobayashi N, Kurosawa M, Iwasaki H, Miyake T, Kohda K, Maekawa I, Sasagawa H, Tsustumi Y, Miyagishima T, Tanaka J, Imamura M, Teshima T
    [Rinsho ketsueki] The Japanese journal of clinical hematology 53 (12) 1983 - 1990 0485-1439 2012/12 [Refereed][Not invited]
  • Haruhiko Kashiwazaki, Takae Matsushita, Junichi Sugita, Akio Shigematsu, Kumiko Kasashi, Yutaka Yamazaki, Takashi Kanehira, Takeshi Kondo, Tomoyuki Endo, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Masahiro Imamura, Yoshimasa Kitagawa, Nobuo Inoue
    SUPPORTIVE CARE IN CANCER 20 (5) 933 - 939 0941-4355 2012/05 [Refereed][Not invited]
     
    Severe oral mucositis developed in allogeneic hematopoietic stem cell transplantation (HSCT) accompanies intolerable pain and risk for systemic bacteremia infection. Conventional stem cell transplantation (CST) and reduced-intensity regimens for allogeneic HSCT (RIST) may differently affect the occurrence and severity of oral mucositis. Here, we comparatively examined oral mucositis in patients undergoing CST and that in RIST patients to search for measures to alleviate oral mucositis. We retrospectively analyzed the data of 130 consecutive patients undergoing HSCT (conventional, 60; RIST, 70). Oral mucositis was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. We also investigated the risk factors for severe oral mucositis in each regimen. The incidence of oral mucositis was not significantly different between RIST and CST patients. The use of opioid analgesics to control pain due to oral mucositis was significantly less in patients undergoing RIST compared with those receiving CST. The risk factors for severe oral mucositis, determined by univariate and multivariate analyses, were "younger age (<40)" in CST and "longer duration of neutropenia (>= 14 days)" in RIST. Although the incidences of oral mucositis were almost the same, the need for opioid analgesics and the risk factors for severe oral mucositis differed between CST and RIST patients.
  • Young Kim, Sanna-Marie Gast, Tomoyuki Endo, Desheng Lu, Dennis Carson, Ingo G. H. Schmidt-Wolf
    LEUKEMIA RESEARCH 36 (5) 598 - 600 0145-2126 2012/05 [Refereed][Not invited]
     
    It was recently confirmed that the diuretic agent ethacrynic acid (EA) inhibits Wnt/beta catenin signaling in myeloma. This study investigated the antitumor effect of EA in vivo in a murine myeloma model. In vivo, tumor growth was significantly reduced and overall survival significantly prolonged in mice treated with EA as compared to untreated mice. Interestingly, this effect was higher as compared to the effect by lenalidomide, a commonly used drug against myeloma. These results reveal a significant in vivo effect by EA against myeloma. (C) 2012 Elsevier Ltd. All rights reserved.
  • Haruhiko Kashiwazaki, Takae Matsushita, Junichi Sugita, Akio Shigematsu, Kumiko Kasashi, Yutaka Yamazaki, Takashi Kanehira, Satoshi Yamamoto, Takeshi Kondo, Tomoyuki Endo, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Masahiro Imamura, Yoshimasa Kitagawa, Nobuo Inoue
    SUPPORTIVE CARE IN CANCER 20 (2) 367 - 373 0941-4355 2012/02 [Refereed][Not invited]
     
    Little is known about the effects of professional oral health care (POHC) on the outcome of hematopoietic stem cell transplantation (HSCT). We evaluated the effects of POHC given by dentists and dental hygienists on the development of oral mucositis and febrile neutropenia (FN) after allogeneic bone marrow transplantation (BMT).We retrospectively studied 140 adult patients who had received allogeneic BMT, with or without POHC, in our hospital consecutively between February 2002 and December 2009. Oral mucositis was evaluated according to the World Health Organization scale.The incidence of oral mucositis was 66.7% (52/78) in the patients who had received POHC, compared to 93.5% (58/62) in the non-POHC group (P < 0.001). The incidence of FN and the maximal level of CRP were also significantly lower in the POHC group. Multivariate analysis revealed that the POHC was significantly associated with the incidence of oral mucositis (odds ratio, 7.58; 95%CI, 2.45-23.34; P < 0.001).We concluded that POHC reduced the incidences of oral mucositis and FN by upgrading the overall oral hygiene during HSCT.
  • Toshihiro Matsukawa, Hideki Goto, Kenta Takahashi, Shinsuke Asanuma, Atsushi Yasumoto, Mutsumi Takahata, Akio Shigematsu, Tomoyuki Endo, Junji Tanaka, Satoshi Hashino, Shinya Tanaka, Masahiro Imamura
    INTERNATIONAL JOURNAL OF HEMATOLOGY 95 (2) 217 - 222 0925-5710 2012/02 [Refereed][Not invited]
     
    Cytomegalovirus (CMV) infection is latent in the majority of adult humans. The reactivation of CMV causes pneumonia and gastrointestinal disease in severely immunosuppressed patients, who consequently suffer very high mortality due to CMV central nervous system disease. We report here a case involving a 28-year-old female patient with mycosis fungoides who underwent umbilical cord blood transplantation three times and developed CMV ventriculoencephalitis. The patient's CMV viremia was successfully preempted with ganciclovir (GCV) as indicated by undetectable CMV antigenemia; despite this successful treatment, the patient developed CMV ventriculoencephalitis. Foscarnet (FCV) therapy led to a temporary recovery, after which CMV ventriculoencephalitis recurred, and the patient died after receiving combination GCV and FCV therapy. Autopsy samples revealed CMV ventriculoencephalitis, as indicated by numerous inclusion-bearing cells (Owl's eye). It is likely that this patient harbored a GCV-resistant CMV strain; however, it was not possible to obtain nucleic acids suitable for use in assessing this possibility.
  • Kim Y, Schmidt M, Endo T, Lu D, Carson D, Schmidt-Wolf IG
    In vivo (Athens, Greece) 6 25 887 - 893 0258-851X 2011/11 [Refereed][Not invited]
  • Ikumi Kasahara, Mitsufumi Nishio, Tomoyuki Endo, Katsuya Fujimoto, Takao Koike, Naomi Sugimori, Takamasa Katagiri, Shinji Nakao
    LEUKEMIA RESEARCH 35 (9) E147 - E148 0145-2126 2011/09 [Refereed][Not invited]
  • Young Kim, Petra Alpmann, Sabine Blaum-Feder, Simon Kraemer, Tomoyuki Endo, Desheng Lu, Dennis Carson, Ingo G. H. Schmidt-Wolf
    LEUKEMIA RESEARCH 35 (8) 1070 - 1073 0145-2126 2011/08 [Refereed][Not invited]
     
    We recently confirmed that ciclopirox olamine inhibits Wnt/beta catenin signalling in myeloma. Griseofulvin (GF) has similar chemical features as compared to ciclopirox olamine. In this study the anti-tumor effect of GF was investigated. GF demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines as well as in human primary cells. In vivo, tumor growth as well as overall survival were significantly reduced in mice treated with GF as compared to untreated mice. In conclusion, our results reveal a significant selective induction of apoptosis by GF and suggest a significant in vivo effect against myeloma. (C) 2010 Elsevier Ltd. All rights reserved.
  • Schmidt M, Kim Y, Gast SM, Endo T, Lu D, Carson D, Schmidt-Wolf IG
    In vivo (Athens, Greece) 3 25 325 - 333 0258-851X 2011/05 [Refereed][Not invited]
  • Masahiro Onozawa, Kazumasa Ohmura, Makoto Ibata, Junko Iwasaki, Kohei Okada, Ikumi Kasahara, Keisuke Yamaguchi, Kanako Kubota, Shinichi Fujisawa, Akio Shigematsu, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Junji Tanaka, Yoshihiro Matsuno, Masahiro Asaka, Masahiro Imamura
    EUROPEAN JOURNAL OF HAEMATOLOGY 86 (4) 347 - 349 0902-4441 2011/04 [Refereed][Not invited]
  • Kanda M, Shigematsu A, Okada K, Kasahara I, Iwasaki J, Yamaguchi K, Onozawa M, Endo T, Akizawa K, Ishiguro N, Hashino S, Imamura M
    [Rinsho ketsueki] The Japanese journal of clinical hematology 3 52 (3) 118 - 123 0485-1439 2011/03 [Refereed][Not invited]
  • Young Kim, Guido Reifenberger, Desheng Lu, Tomoyuki Endo, Dennis A. Carson, Sanna-Marie Gast, Karoline Meschenmoser, Michael Nowak, Ingo G. H. Schmidt-Wolf
    ANTICANCER RESEARCH 31 (2) 725 - 730 0250-7005 2011/02 [Refereed][Not invited]
     
    Recent studies have implicated genetic and epigenetic aberrations resulting in aberrant activation of the Wingless-Int (Wnt) pathway and thus influencing the initiation and progression of multiple myeloma (MM). Of major importance, these findings may lead to novel treatment strategies exploiting targeted modulation of Wnt signaling. This review describes the current status of knowledge concerning the role of Wnt pathway alteration in MM and outlines future lines of research and their clinical perspectives.
  • Kim Y, Alpmann P, Blaum-Feder S, Krämer S, Endo T, Lu D, Carson D, Schmidt-Wolf IG
    In vivo (Athens, Greece) 1 25 99 - 103 0258-851X 2011/01 [Refereed][Not invited]
  • Mutsumi Takahata, Satoshi Hashino, Kohei Okada, Masahiro Onozawa, Kaoru Kahata, Junichi Sugita, Akio Shigematsu, Takeshi Kondo, Satoshi Yamamoto, Tomoyuki Endo, Mitsufumi Nishio, Yoichi M. Ito, Junji Tanaka, Takao Koike, Masahiro Asaka, Masahiro Imamura
    AMERICAN JOURNAL OF HEMATOLOGY 85 (4) 243 - 248 0361-8609 2010/04 [Refereed][Not invited]
     
    Reduced intensity conditioning (RIC) regimens are widely used in allogeneic stem cell transplantation (SCT). In this study, we retrospectively investigated the clinical outcomes of RIC with fludarabine (Flu; 180 mg/m(2)), intravenous busulfan (BU; 6.4 mg/kg) or oral BU (8 mg/kg), and low-dose total body irradiation (TBI; 4 Gy) (Flu-BU2-TBI) in 66 patients (median age: 54.5 years) with various hematological malignancies. Thirty-eight patients (58%) were high-risk patients (median age: 56 years). The overall survival rate at 2 years of the high-risk patients was 64.5%, which was comparable to the survival rate of 70.9% in standard-risk patients (P = 0.68). The relapse rates at 2 years in the standard-risk and high-risk patients were 16 and 28%, respectively, and day 100 treatment-related mortality rates were 0 and 6%, respectively. The Flu-BU2-TBI regimen for high-risk patients showed therapeutic effects equivalent to those for standard-risk patients and favorable outcomes compared with those of other previous RIC regimens. Am. J. Hematol. 84:243-248, 2010. (C) 2010 Wiley-Liss, Inc.
  • Lei Wang, Hiroshi Nishihara, Taichi Kimura, Yasutaka Kato, Mishie Tanino, Mitsufumi Nishio, Masato Obara, Tomoyuki Endo, Takao Koike, Shinya Tanaka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 395 (1) 111 - 115 0006-291X 2010/04 [Refereed][Not invited]
     
    DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines, Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy. (C) 2010 Elsevier Inc. All rights reserved.
  • Takeshi Kondo, Atsushi Yasumoto, Kotaro Arita, Jun-ichi Sugita, Akio Shigematsu, Kohei Okada, Mutsumi Takahata, Masahiro Onozawa, Kaoru Kahata, Yukari Takeda, Masato Obara, Satoshi Yamamoto, Tomoyuki Endo, Mitsufumi Nishio, Norihiro Sato, Junji Tanaka, Satoshi Hashino, Takao Koike, Masahiro Asaka, Masahiro Imamura
    INTERNATIONAL JOURNAL OF HEMATOLOGY 91 (2) 310 - 321 0925-5710 2010/03 [Refereed][Not invited]
     
    Acute myelogenous leukemia (AML) with favorable cytogenetics responds well to chemotherapy. If the leukemia relapses, allogenic hematopoietic stem transplantation (allo-HSCT) is considered as a treatment option. Since the efficacy of reduced-intensity stem cell transplantation (RIST) for AML with favorable cytogenetics has not been established, we retrospectively analyzed the outcomes of allo-HSCT in AML patients according to cytogenetic risks. The outcome of allo-HSCT for AML patients with favorable cytogenetics seemed to be superior to that for AML patients with intermediate cytogenetics. In AML patients with favorable cytogenetics, the 3-year overall survival (OS) and relapse-free survival (RFS) rates were 88 and 76%, respectively, in the RIST group. Both the 3-year OS and RFS rates were 81% in the conventional stem cell transplantation (CST) group. The outcome of RIST for AML patients with favorable cytogenetics was comparable to that for patients who received CST despite the more advanced age and greater organ dysfunction in RIST group than in CST group. None of the patients died within 90 days after RIST. Moreover, there was no relapse in patients with favorable cytogenetics who were in hematological remission prior to RIST. Thus, RIST for AML patients with favorable cytogenetics in remission is safe and effective.
  • Katsuya Fujimoto, Tomoyuki Endo, Mitsufumi Nishio, Masato Obara, Keisuke Yamaguchi, Yukari Takeda, Hideki Goto, Ikumi Kasahara, Norihiro Sato, Takao Koike
    INTERNATIONAL JOURNAL OF HEMATOLOGY 90 (5) 601 - 604 0925-5710 2009/12 [Refereed][Not invited]
     
    A 44-year-old female presented with asymptomatic leukocytosis and moderate splenomegaly. The diagnosis of splenic marginal zone lymphoma (SMZL) was made by a splenectomy. A virological examination revealed the patient to be a hepatitis B virus (HBV) carrier. The lymphocyte count in her peripheral blood decreased after splenectomy, but remained high for 2 years and bone marrow infiltration was obvious. Two years after the splenectomy, she was admitted for an acute flare-up of hepatitis B. The liver dysfunction improved without any medication and thereafter returned to the normal range within a few weeks. At the same time, the lymphocyte count in her peripheral blood rapidly decreased to normal levels. Atypical lymphocytes disappeared from the peripheral blood and bone marrow aspirates and biopsy specimen revealed complete remission of SMZL, including the disappearance of the clonal rearrangement of IgH-JH. There has been no recurrence of acute hepatitis and she has been in complete remission for SMZL for more than 6 years. The clinical course of this patient suggests that an immune response against HBV also affects the clearance of lymphoma cells. This is the first report that a complete remission was achieved in a patient with SMZL after a hepatitis B flare-up.
  • Desheng Lu, Jerry X. Liu, Tomoyuki Endo, Haowen Zhou, Shiyin Yao, Karl Willert, Ingo G. H. Schmidt-Wolf, Thomas J. Kipps, Dennis A. Carson
    PLOS ONE 4 (12) e8294  1932-6203 2009/12 [Refereed][Not invited]
     
    Background: Aberrant activation of Wnt/beta-catenin signaling promotes the development of several cancers. It has been demonstrated that the Wnt signaling pathway is activated in chronic lymphocytic leukemia (CLL) cells, and that uncontrolled Wnt/beta-catenin signaling may contribute to the defect in apoptosis that characterizes this malignancy. Thus, the Wnt signaling pathway is an attractive candidate for developing targeted therapies for CLL. Methodology/Principal Findings: The diuretic agent ethacrynic acid (EA) was identified as a Wnt inhibitor using a cell-based Wnt reporter assay. In vitro assays further confirmed the inhibitory effect of EA on Wnt/beta-catenin signaling. Cell viability assays showed that EA selectively induced cell death in primary CLL cells. Exposure of CLL cells to EA decreased the expression of Wnt/beta-catenin target genes, including LEF-1, cyclin D1 and fibronectin. Immune co-precipitation experiments demonstrated that EA could directly bind to LEF-1 protein and destabilize the LEF-1/beta-catenin complex. N-acetyl-L-cysteine (NAC), which can react with the a, beta-unsaturated ketone in EA, but not other anti-oxidants, prevented the drug's inhibition of Wnt/beta-catenin activation and its ability to induce apoptosis in CLL cells. Conclusions/Significance: Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/beta-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease.
  • Ikumi Kasahara, Mitsufumi Nishio, Satoshi Yamamoto, Tomoyuki Endo, Katsuya Fujimoto, Keisuke Yamaguchi, Yukari Takeda, Hideki Goto, Norihiro Sato, Takao Koike
    INTERNATIONAL JOURNAL OF HEMATOLOGY 90 (3) 413 - 415 0925-5710 2009/10 [Refereed][Not invited]
     
    Two multiple myeloma patients relapsed after autologous stem cell transplantation (ASCT). Conventional chemotherapy, including thalidomide, showed very little effect, but both patients responded well to a standard dose of bortezomib. One patient was treated with two additional cycles of bortezomib, but his clinical course suddenly deteriorated. Unrelated cord blood transplantation (CBT) with reduced-intensity conditioning regimen (RIC) was performed in refractory disease. After CBT, the clinical course was aggravated by tumor lysis syndrome and other conditions, thus resulting in patient death on day 34. Thereafter, we administered CBT with RIC on the second patient after just one course of bortezomib therapy since she was in partial remission. The second patient developed acute and chronic GVHD, and both responded to the steroid therapy. She has been in complete remission for more than 48 months after CBT. These results suggested that the timing of CBT with RIC may be very important, and cytoreduction with not only ASCT but also bortezomib could give a promising chance for a successful CBT.
  • Tomoyuki Endo, Katsuya Fujimoto, Mitsufumi Nishio, Satoshi Yamamoto, Masato Obara, Norihiro Sato, Takao Koike
    JOURNAL OF MEDICAL VIROLOGY 81 (6) 979 - 982 0146-6615 2009/06 [Refereed][Not invited]
     
    The effect of highly active antiretroviral therapy (HAART) on hepatitis C virus (HCV) infection remains uncertain. This report describes the case of a man with hemophilia with HIV-HCV coinfection with persistent disappearance of HCV RNA after changing the HAART regimen. He had been treated with zidovudine, lamivudine, and indinavir for initial HAART and the HIV RNA level had been undetectable for more than 8 years. He had Suffered from chronic active hepatitis. The HAART regimen was changed to emtricitabine/tenofovir, atazanavir, and ritonavir because the patient preferred a once daily regimen. The HCV RNA level fell immediately and thereafter became undetectable by quantitative and qualitative assay at 5 and 7 months after the change of the HAART regimen, respectively. In contrast to other reported cases, he experienced neither increase of CD4+ T cells Count nor ALT flare-ups before HCV RNA clearance. The HCV RNA disappearance in this case may be due to the direct effect of HAART against HCV rather than restoration of cellular immunity to HCV. J. Med. Virol. 81:979-982, 2009. (c) 2009 Wiley-Liss Inc.
  • Akio Shigematsu, Atsushi Yasumoto, Satoshi Yamamoto, Junichi Sugita, Takeshi Kondo, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Shuichi Ota, Norihiro Sato, Mutsumi Takahata, Kohei Okada, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Takao Koike, Masahiro Asaka, Masahiro Imamura
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 15 (6) 679 - 685 1083-8791 2009/06 [Refereed][Not invited]
     
    Cytomegalovirus (CMV) infection is I of the major causes of morbidity in patients undergoing allogeneic stem cell transplantation (allo-SCT). The incidences of CMV antigenemia and CMV disease in 43 patients who received allogeneic bone marrow trans plantation (BMT) using a reduced-intensity conditioning (RIC) regimen, which mainly consisted of fluclarabine (Flu), busulfan (Bu), and total body irradiation (TBI), were compared with those in 68 patients who received a myeloablative conditioning (MAC) regimen, and risk factors for CMV antigenemia and CMV disease were identified. Before engraftment, grade 3-4 mucosal injury because of the conditioning regimen was significantly decreased in RIC patients (stomatitis: P=.02; diarrhea: P<.01). Rate of engraftment, incidences of acute graft-versus-host disease (aGVHD), and rate of corticosteroid administration were not different in RIC patients and MAC patients. Although the incidences of CMV antigenemia were not significantly different in RIC patients and MAC patients (64.1% versus 57.8%, log rank, P=.59), the incidence of CMV disease was significantly decreased in RIC patients (5.4% versus 20.3%, log rank, P=.04). CMV seropositivity in the patients (P<.01) and corticosteroid administration (P<.01) were revealed by multivariate analysis to be significant risk factors for CMV antigenemia. Grade II-IV aGVHD (P=.02) and grade 3-4 diarrhea before engraftment (P=.04) were revealed to be risk factors for CMV disease. The present study is the first study to show that severe diarrhea before engraftment is a significant risk factor for CMV disease. In summary, risk of CMV disease was significantly decreased in patients without severe mucosal injury of the gut because of the conditioning regimen before engraftment. Biol Blood Marrow Transplant 15: 679-685 (2009) (C) 2009 American Society for Blood and Marrow Transplantation
  • Matthias Schmidt, Elisabeth Sievers, Tomoyuki Endo, Desheng Lu, Dennis Carson, Ingo G. H. Schmidt-Wolf
    BRITISH JOURNAL OF HAEMATOLOGY 144 (5) 796 - 798 0007-1048 2009/03 [Refereed][Not invited]
  • Mitsufumi Nishio, Tomoyuki Endo, Katsuya Fujimoto, Satoshi Yamamoto, Masato Obara, Keisuke Yamaguchi, Yukari Takeda, Hideki Goto, Ikumi Kasahara, Norihiro Sato, Takao Koike
    EUROPEAN JOURNAL OF HAEMATOLOGY 82 (2) 143 - 147 0902-4441 2009/02 [Refereed][Not invited]
     
    Recent studies have indicated that patients who receive stem cell transplantation (SCT) and rituximab demonstrate an increased risk of developing hypogammaglobulinemia. Such hypogammaglobulinemia has been found to be due to delayed recovery of memory B cells with an abnormal cell marker expression and impaired immunoglobulin production in vitro. However, no predictive factors for the levels of immunoglobulin after autologous SCT and rituximab therapy have been reported. The aim of this study is to clarify the relationships between the FCGR3A-158V/F genotype and the levels of serum immunoglobulin after SCT. A total of 24 non-Hodgkin's lymphoma (NHL) patients received autologous SCT with an adjuvant rituximab. The FCGR3A-158V/F genotype was determined in these patients. We also included ten NHL patients who received an identical conditioning regimen and autologous SCT but no rituximab as control patients. The levels of IgG were significantly lower in FCGR3A-158F homozygous patients (n = 9) in comparison to those in FCGR3A-158V carriers (n = 15). Moreover, the levels of IgG and IgA of FCGR3A-158F homozygous patients, but not those of FCGR3A-158V carriers, were significantly lower than those of control patients. The genotype of FCGR3A determines not only the response to rituximab, but also the levels of immunoglobulin after SCT and an adjuvant rituximab.
  • Akio Shigematsu, Takeshi Kondo, Satoshi Yamamoto, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Soichi Shiratori, Shuichi Ota, Masato Ohara, Kentaro Wakasa, Mutsumi Takahata, Yukari Takeda, Junji Tanaka, Satoshi Hashino, Mitsufumi Nishio, Takao Koike, Masahiro Asaka, Masahiro Imamura
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 14 (5) 568 - 575 1083-8791 2008/05 [Refereed][Not invited]
     
    We retrospectively evaluated the outcomes of 37 adult patients with acute lymphoblastic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) conditioned with medium-dose VP-16 (VP, 30 mg/kg), cyclophosphamide, (CY, 120 mg/kg), and fractionated total-body irradiation (TBI, 12 Gy) (medium-dose VP/CY/TBI). The median age of the patients was 26 years. Thirteen patients underwent transplantation from HLA-matched related donors (MRD), 18 patients underwent transplantation from HLA-matched unrelated donors (MUD), and 6 patients underwent transplantation from HLA-mismatched donors (MMD). Thirty-two patients received bone marrow and 4 patients received peripheral blood stem cells. Ten patients were Philadelphia chromosome-positive (Ph+) and 35 patients were in complete remission (CR) at transplantation. All of the patients achieved engraftment, and grade 3 organ toxicity before engraftment occurred in 27 patients. Grade H-M acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15 and 18 patients, respectively. No patient developed grade IV acute GVHD (aGVHD) or died of GVHD. At median follow-up of 35.1 months, 32 patients were alive and all Ph+ patients were alive. Three patients died of relapse and 2 died of transplant-related mortality (TRM). The actuarial 3-year overall survival (OS) rate, relapse rate, and TRM rate were 89.2%, 8.1%, and 5.4%, respectively. Non-CR at transplantation, MRD, and no aGVHD were significant adverse prognostic factors for survival. Medium-dose VP/CY/TBI for adult ALL patients was associated with lower relapse rate and no increase in toxicity, resulting in better survival. (C) 2008 American Society for Blood and Marrow Transplantation.
  • Tetsuya Fukuda, Liguang Chen, Tomoyuki Endo, Li Tang, Desheng Lu, Jariuario E. Castro, George F. Widhopf, Laura Z. Rassenti, Mark J. Cantwell, Charles E. Prussak, Dennis A. Carson, Thomas J. Kipps
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 (8) 3047 - 3052 0027-8424 2008/02 [Refereed][Not invited]
     
    We examined the sera of six patients before and after i.v. infusions of autologous chronic lymphocytic leukemia (CLL) cells transduced ex vivo with an adenovirus encoding CD154 (Ad-CD154). Five patients made high-titer antibodies against adenovirus and three made IgG reactive with a leukemia-associated surface antigen, which we identified as ROR1. Anti-ROR1 antibodies were not detected in the sera of untreated patients. We generated anti-ROR1 mAbs and found they reacted specifically with the CLL cells of all patients, but not with nonleukemic leukocytes, a wide variety of normal adult tissues, or blood mononuclear cells, including CD5(+) B cells of healthy adults. ROR1 could bind Wnt5a, which induced activation of NF-kappa B when coexpressed with ROR1 in HEK293 cells and enhanced the survival of CLL cells in vitro, an effect that could be neutralized by posttreatment anti-ROR1 antisera. We conclude that patients with CLL can break immune tolerance to ROR1, which is an oncofetal surface antigen and survival-signaling receptor in this neoplastic disease.
  • Mitsufumi Nishio, Katsuya Fujimoto, Satoshi Yamamoto, Tomoyuki Endo, Toshiya Sakai, Masato Obara, Kohki Kumano, Keisuke Yamaguchi, Yukari Takeda, Hideki Goto, Norihiro Sato, Kazuki Koizumi, Masaya Mukai, Takao Koike
    BRITISH JOURNAL OF HAEMATOLOGY 137 (4) 349 - 354 0007-1048 2007/05 [Refereed][Not invited]
     
    Recent studies have indicated that patients who received rituximab as an adjuvant to stem cell transplantation (SCT) demonstrated an increased risk of developing severe hypogammaglobulinaemia, which was found to be a result of delayed recovery of CD27 positive memory B cells and impaired isotype expression. It appears that rituximab influences both the quantity and quality of B-cell redistribution. Precisely how the B-cell repertoire regenerates after anti-CD20-mediated transient B-cell depletion in patients with non-Hodgkin lymphoma (NHL) remains to be elucidated. This study performed a phenotypical analysis of B cells in 17 NHL patients who received rituximab as an adjuvant to autologous SCT. The median period after final administration of rituximab was 36 months (range, 12-43 months). Surface antigen expression of CD27, CD40 and CD80 in NHL patients was statistically significantly different from healthy controls (n = 14). Moreover, B cells from NHL patients showed significantly impaired IgG and IgA production upon engagement of surface immunoglobulin receptors in the presence of interleukin (IL)-2, IL-10 and CD40 ligand in comparison with samples from healthy controls. The delayed recovery of memory B cells with an abnormal cell marker expression and function demonstrates that naive B cells may fail to differentiate into plasma cells, resulting in hypogammaglobulinaemia after autologous SCT and rituximab therapy.
  • Masahiko Shigemura, Takanori Moriyama, Hitoshi Shibuya, Masato Obara, Tomoyuki Endo, Satoshi Hashino, Hiroshi Yokouchi, Masahiro Asaka, Chikara Shimizu, Hitoshi Chiba, Masaharu Nishimura
    CLINICA CHIMICA ACTA 376 (1-2) 121 - 125 0009-8981 2007/02 [Refereed][Not invited]
     
    Background: There have been several reports describing a notable hyperamylasaemia in patients with multiple myeloma. Such amylase-producing myelomas have been mainly described in the context of concomitant salivary-type hyperamylasaemia, with sialyl salivary-type amylase identified in a portion of those cases. We investigated the incidence of the production of sialyl salivary-type amylase in serum of multiple myeloma patients. Methods: Eleven patients (6 male and 5 female) who had been diagnosed as having multiple myeloma were enrolled in this study. Sialyl salivary-type amylase was detected by isoamylase electrophoresis and HPLC analysis, and identified by detecting either abnormal neuraminidase-sensitive band through isoamylase electrophoresis or abnormal extra-elution peak of amylase by means of HPLC analysis. Results: Sialyl salivary-type amylase was detected in 7 out of 11 (63.6%) patients. Median total amylase activity was 154 U/l (range 109-43020). Isoamylase electrophoretic patterns of patients' serum were normal in 5 patients (71.4%) out of 7 patients and salivary-dominant in 2 (50.0%) out of 4 patients. Conclusions: We consider that there is no significant relationship between total serum amylase level and amylase isoenzyme pattern in the incidence of production of sialyl salivary-type amylase with multiple myeloma. (c) 2006 Elsevier B.V. All rights reserved.
  • Tomoyuki Endo, Mitsufumi Nishio, Thomas Enzler, Howard B. Cottam, Tetsuya Fukuda, Danelle F. James, Michael Karin, Thomas J. Kipps
    BLOOD 109 (2) 703 - 710 0006-4971 2007/01 [Refereed][Not invited]
     
    Chronic lymphocytic leukemia (CLL) B cells express BR3, the specific receptor for the B cell-activating factor of tumor necrosis factor family (BAFF). CLL cells also express 2 other receptors for BAFF, namely B-cell maturation antigen (BCMA) and the transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI), which also bind a proliferation-inducing ligand (APRIL). We found that signaling through BR3, but not BCMA or TACI, activated the alternative nuclear factor of kappa B (NF-kappa B) pathway in CLL cells, whereas signaling through BCMA/ TACI induced activation of the canonical NF-kappa B pathway. Blocking BR3 did not inhibit the capacity of BAFF to support CLL cell survival in vitro. On the other hand, specifically blocking the canonical NF-kappa B pathway with LITC, an inhibitor of I kappa B kinase beta (IKK beta), or transfection of CLL cells with the I kappa B alpha super-repressor, blocked the capacity of BAFF and APRIL to promote CLL cell survival in vitro. This contrasts what is found with normal blood B cells, which apparently depend on activation of the alternative NF-kappa B pathway for BAFF-enhanced survival. These findings suggest that inhibitors of protein kinase IKK beta, which is required for activation of the canonical NF-kappa B pathway, might have a therapeutic role in this disease. (c) 2007 by The American Society of Hematology
  • Mitsufumi Nishio, Katsuya Fujimoto, Satoshi Yamamoto, Tomoyuki Endo, Toshiya Sakai, Masato Obara, Kohki Kumano, Koichiro Minauchi, Keisuke Yamaguchi, Yukari Takeda, Norihiro Sato, Kazuki Koizumi, Masaya Mukai, Takao Koike
    EUROPEAN JOURNAL OF HAEMATOLOGY 77 (3) 226 - 232 0902-4441 2006/09 [Refereed][Not invited]
     
    Objectives: Some studies have indicated patients who received rituximab as adjuvant to stem cell transplantation had an increased risk of developing severe hypogammaglobulinemia. The mechanism of this hypogammaglobulinemia is unknown, although investigators have hypothesized a further delay in the B-cell recovery as one potential etiology. The aim of this study is to clarify the mechanism(s) of this hypogammaglobulinemia. Methods: A total of 14 patients with high-risk CD20(+) lymphoma underwent an autologous peripheral blood stem cell transplantation (APBSCT). After a hematological recovery, rituximab was given weekly for up to four doses as an adjuvant therapy. Results: After a median follow up of 33.5 months, we found six patients (group A) who had hypogammaglobulinemia, while the eight other patients (group B) had normal serum immunoglobulin levels. A phenotypical analysis revealed that group A patients had already achieved B-cell recovery. However, we found a severe delay in the recovery of CD27(+) memory B cells, especially in the IgD(-)/CD27(+) switched populations in group A, but CD27 negative naive B-cells reverted to a normal range in both groups. Consistent with this, reverse transcriptase-polymerase chain reaction studies with peripheral blood mononuclear cells revealed that most patients in group A lacked more than two classes of isotype transcripts. Conclusions: Abnormal repertoires and impaired isotype expression are seen in patients with common variable immunodeficiency, these data suggested that rituximab after APBSCT can affect not only the B-cell quantities, but also the recovery of the B-cell repertoires.
  • T Hashimoto, M Nishio, T Sakai, K Fujimoto, N Sato, T Endo, T Koike
    CLINICAL INFECTIOUS DISEASES 42 (11) 1653 - 1655 1058-4838 2006/06 [Refereed][Not invited]
  • M Nishio, T Endo, K Fujimoto, N Sato, T Sakai, M Obara, K Kumano, K Minauchi, T Koike
    EUROPEAN JOURNAL OF HAEMATOLOGY 75 (6) 527 - 529 0902-4441 2005/12 [Refereed][Not invited]
  • A Takami, H Okumura, H Yamazaki, M Kami, SW Kim, H Asakura, T Endo, M Nishio, K Minauchi, K Kumano, N Sugimori, S Mori, Y Takemoto, S Shimadoi, J Ozaki, Y Takaue, S Nakao
    INTERNATIONAL JOURNAL OF HEMATOLOGY 82 (5) 449 - 455 0925-5710 2005/12 [Refereed][Not invited]
     
    To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-close cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.
  • M Nishio, T Endo, N Tsukada, J Ohata, S Kitada, JC Reed, NJ Zvaifler, TJ Kipps
    BLOOD 106 (3) 1012 - 1020 0006-4971 2005/08 [Refereed][Not invited]
     
    We examined expression of B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic lymphocytic leukemia (CLL) B cells and nurselike cells (NLCs), which differentiate from CD14(+) cells when cultured with CLL B cells. NLCs expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells cultured with NLCs was significantly reduced when CLL B cells were cultured with decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and APRIL, but not with BAFF receptor:Fc (BAFF-R:Fc), which binds only to BAFF. The effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and distinct from that of stromal cell-derived factor-1 alpha (SDF1 alpha), which in contrast to BAFF or APRIL induced leukemia cell phosphorylation of p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase-1/2 [ERK1/2]) and AKT. Conversely, BAFF and APRIL, but not SDF-1 alpha, induced CLL-cell activation of the nuclear factor-kappa B1 (NF-kappa B1) and enhanced CLL-cell expression of the antiapoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL-cell activation of NF-kappa B2. We conclude that BAFF and APRIL from NLCs can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1 alpha, indicating that NLCs use multiple distinct pathways to support CLL-cell survival.
  • Nomura T, Abe R, Fujimoto K, Endo T, Shimizu H, Koike T
    AIDS (London, England) 18 18 2446 - 2448 0269-9370 2004/12 [Refereed][Not invited]
  • H Fukaya, WG Xiao, K Inaba, Y Suzuki, M Hirokawa, Y Kawabata, A Komatsuda, T Endo, H Kishimoto, G Takada, K Sawada
    EXPERIMENTAL HEMATOLOGY 32 (5) 450 - 460 0301-472X 2004/05 [Refereed][Not invited]
     
    Objective. Tumor necrosis factor-alpha (TNF-alpha) inhibits erythropoiesis and enhances nonerythroid colony formation. The present study examines the nature of these nonerythroid cells and investigates their physiologic role in relation to erythroid progenitor cells. Materials and Methods. Highly purified human CD34(+) cells underwent erythroid differentiation in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3), and erythropoietin (EPO), with and without TNF-alpha. We enumerate colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells in semisolid phase as well as in liquid suspension culture. The character and roles of codeveloping nonerythroid cells in the presence of TNF-alpha were analyzed using fluorescent activating cell sorter, enzyme immunohistochemistry, and confocal microscopy. Results. TNF-alpha inhibited the generation of GPA(+) cells and conversely enhanced the generation of GPA(-) cells. The GPA(-) cells were comprised of cells with excentric cell shape and were positive for HLA class I, HLA class II, CD1a, CD4, CD11c, CD14, CD40, CD80, CD83, and CD86, but not for CD3, CD8, CD19, CD20, and CD56, indicating the codevelopment of dendritic cells (DC) along with erythroid differentiation. Developing DC/DC precursors were detected within 3 days of culture. Only in the presence of TNF-alpha did CD34(+) cells proliferate by forming aggregates where both GPA(+) and CD11c(+) DC/DC precursors were present. During culture period, immature CD11c(+) DC were capable of endocytosing damaged GPA(+) cells. Conclusions. GPA(-) cells cogenerated from human CD34(+) cells during erythroid differentiation in the presence of IL-3/SCF/EPO and TNF-alpha express DC phenotypes. The CD11c(+) DC subset physically and selectively associates with developing immature erythroid cells and damaged self-GPA(+) cells and then obtains and captures self-substances. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.
  • K Koizumi, K Fujimoto, Y Haseyama, T Endo, M Nishio, K Yokota, T Itoh, K Sawada, T Koike
    EUROPEAN JOURNAL OF HAEMATOLOGY 72 (2) 140 - 144 0902-4441 2004/02 [Refereed][Not invited]
     
    The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous involvement especially is morbid despite intensive chemotherapy and radiotherapy. We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T-cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were administered and complete remission (CR) was attained. High-dose chemotherapy (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then prescribed. Complete remission (CR) was obtained and she has been free of disease for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy facilitated by autologous stem cell transplantation should be considered part of the primary therapy for subjects with a poor prognosis for nasal NK/T-cell lymphoma with cutaneous involvement.
  • M Shigemura, T Moriyama, T Endo, H Shibuya, H Suzuki, M Nishimura, H Chiba, K Matsuno
    CLINICAL CHEMISTRY AND LABORATORY MEDICINE 42 (6) 677 - 680 1434-6621 2004 [Refereed][Not invited]
  • WG Xiao, K Koizumi, M Nishio, T Endo, M Osawa, K Fujimoto, Sato, I, T Sakai, T Koike, K Sawada
    EXPERIMENTAL HEMATOLOGY 30 (11) 1238 - 1247 0301-472X 2002/11 [Refereed][Not invited]
     
    Objective. The inhibitory effects of tumor necrosis factor-alpha (TNF-alpha) on cytokine-induced proliferation and differentiation of normal human erythroid progenitors have been characterized extensively, yet little is known about the maturation level of erythroid progenitors that are sensitive to TNF-alpha or of the expression of TNF receptors (TNFRs) in erythroid lineage. The aim of this study was to determine the extent to which human erythroid progenitor cells are sensitive to TNF-alpha, and to relate this to the expression of TNFRs in the erythroid lineage. Materials and Methods. Highly purified human CD34(+) cells underwent erythroid differentiation, with or without TNF-alpha. We used colony assay as well as a method by which colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells can be generated in liquid phase from purified human CD34(+) cells in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3), and erythro-poietin (EPO). During erythroid differentiation of CD34(+) cells, TNFRs expression were monitored. Results. TNF-alpha inhibited the generation of GPA(+) cells by CD34(+) cells as well as the proliferative capacity of GPA(+) cells supported by EPO, IL-3, and SCF. Erythroid progenitors became resistant to the inhibitory effect of TNF-alpha as they matured. The detectable expression of TNFR-I was transient in the early phase of erythroid differentiation, whereas TNFR-II was expressed through the entire course of erythroid differentiation of CD34(+) cells. Conclusions. TNF-alpha suppresses erythropoiesis by inhibiting the generation of GPA(+) cells derived from CD34(+) cells as well as by inhibiting the proliferative capacity of GPA(+) cells. Although the presence of TNFRs does not directly indicate that the receptor(s) mediates death signaling, altered expression of TNFRs depending on the level of maturation may imply altered sensitivities to TNF-alpha in various stage of erythroid progenitors. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.

MISC

  • IgA型ALアミロイドーシスに線状IgA皮膚症を併発した1例
    山口 泰之, 氏家 英之, 大東 寛幸, 岩田 浩明, 村松 憲, 清水 宏, 遠藤 知之, 豊嶋 崇徳  日本皮膚科学会雑誌  127-  (9)  2111  -2111  2017/08  [Not refereed][Not invited]
  • 当院においてドナーリンパ球輸注を施行した34症例の検討
    石尾 崇, 立野 貴大, 笠原 耕平, 小杉 瑞葉, 白鳥 聡一, 岡田 耕平, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 遠藤 知之, 近藤 健, 豊嶋 崇徳  日本輸血細胞治療学会誌  63-  (2)  148  -149  2017/04  [Not refereed][Not invited]
  • HIV/HCV重複感染者に対するソホスブビルを投与(多施設共同研究)
    四柳 宏, 遠藤 知之, 塚田 訓久, 潟永 博之, 三田 英治, 菊地 正, 鯉渕 智彦, 木村 哲  感染症学雑誌  91-  (臨増)  278  -278  2017/03  [Not refereed][Not invited]
  • 胆嚢炎症状を契機に発症したTAFRO症候群
    関根 隆博, 後藤 秀樹, 日高 大輔, 早瀬 英子, 小杉 瑞葉, 岡田 耕平, 白鳥 総一郎, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 遠藤 知之, 近藤 健, 豊嶋 崇徳  臨床血液  57-  (12)  2608  -2608  2016/12  [Not refereed][Not invited]
  • 肺胞蛋白症を合併し致死的な経過を辿った骨髄異形成症候群の1例
    大東 寛幸, 松川 敏大, 金谷 穣, 後藤 秀樹, 橋本 大吾, 加畑 馨, 遠藤 知之, 田中 伸哉, 豊嶋 崇徳  臨床血液  57-  (11)  2398  -2398  2016/11  [Not refereed][Not invited]
  • HIV感染症合併血友病患者に対するMRIによる脳スクリーニングの意義
    遠藤 知之, 宮下 直洋, 笠原 耕平, 小杉 瑞葉, 岡田 耕平, 白鳥 聡一, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 近藤 健, 橋野 聡, 豊嶋 崇徳  日本エイズ学会誌  18-  (4)  439  -439  2016/11  [Not refereed][Not invited]
  • 多職種で連携して診療にあたったHIV合併妊娠管理についての検討
    金川 明功, 小島 崇史, 山田 崇弘, 長 和俊, 遠藤 知之, 西村 あや子, 石川 聡司, 森川 守, 山田 俊, 近藤 健, 水上 尚典  北日本産科婦人科学会総会・学術講演会プログラム・抄録集  64回-  145  -145  2016/09  [Not refereed][Not invited]
  • 当院における同種末梢血幹細胞採取の検討
    杉田 純一, 大東 寛幸, 橋口 淳一, 松川 敏大, 金谷 穣, 小杉 瑞葉, 松岡 里湖, 後藤 秀樹, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 遠藤 知之, 近藤 健, 豊嶋 崇徳  日本輸血細胞治療学会誌  62-  (3)  490  -490  2016/06  [Not refereed][Not invited]
  • 【エイズの臨床 アップデート】 医療現場における曝露後予防
    遠藤 知之  アレルギー・免疫  23-  (5)  702  -707  2016/04  [Not refereed][Not invited]
     
    HIV感染者数の増加と患者の高齢化に伴い、様々な施設においてHIV感染者と関わる必要性がでてきている。HIV感染者の診療に際しては、感染対策として特別な対応は必要なく、標準予防策の遵守が基本となる。針刺し等の血液・体液曝露の際には、速やかに抗HIV薬の予防内服を開始することで感染率をほぼゼロにすることができる。HIV曝露後予防の第一推奨薬はTenofovir/Emtricitabine(ツルバダ)とRaltegravir(アイセントレス)の2剤である。いざというときに慌てないために、曝露時の対応マニュアルを各施設で整備しておくことが重要である。(著者抄録)
  • 【すべての内科医のためのHIV感染症-長期管理の時代に】 HIV感染症にまつわるFAQ HIVに求められる感染対策
    遠藤 知之  内科  116-  (5)  815  -819  2015/11  [Not refereed][Not invited]
     
    HIV感染者数の増加と生命予後改善に伴う患者の高齢化に伴い,さまざまな施設/診療科においてHIV感染者と関わる必要性が出てきている.HIV感染者の診療に際しては,感染対策として特別な対応は必要なく,標準予防策(standard precautions)の遵守が基本となる.HIVは,HBVやHCVと比較して感染力が弱いため,医療器具の消毒などもHBVのマニュアルに準じて行うことで十分である.針刺しなどの曝露事故の際には,速やかに抗HIV薬の予防内服を開始することで感染率を下げることができる.いざというときに慌てないために,曝露事故時の対応マニュアルなどを各施設で整備しておくことが重要である.(著者抄録)
  • Cardio-ankle vascular index(CAVI)を用いたHIV感染者の動脈硬化の評価とリスク因子の検討
    遠藤 知之, 宮下 直洋, 笠原 耕平, 渡部 恵子, 武内 阿味, 松川 敏大, 金谷 穣, 小杉 瑞葉, 松岡 里湖, 後藤 秀樹, 杉田 純一, 小野澤 真弘, 橋本 大吾, 加畑 馨, 藤本 勝也, 近藤 健, 橋野 聡, 豊嶋 崇徳  日本エイズ学会誌  17-  (4)  392  -392  2015/11  [Not refereed][Not invited]
  • 初回ART導入におけるRaltegravirとDolutegravirの血液毒性への関与
    後藤 秀樹, 遠藤 知之, 藤本 勝也, 近藤 健, 加畑 馨, 橋本 大吾, 小野澤 真弘, 杉田 純一, 松川 敏大, 笠原 耕平, 宮下 直洋, 橋野 聡, 佐藤 典宏, 豊嶋 崇徳  日本エイズ学会誌  17-  (4)  510  -510  2015/11  [Not refereed][Not invited]
  • 【危惧する感染症-院内感染防止対策-】 HIV感染症
    遠藤 知之  Surgery Frontier  22-  (3)  209  -215  2015/09  [Not refereed][Not invited]
     
    わが国では、新規のHIV感染者/AIDS発症者数が、いまだ低下傾向を示していない。抗HIV薬の進歩にともない患者の生命予後が劇的に改善したこともあり、わが国におけるHIV感染者数は増え続けている。HIV感染者の診療に際しては、特別な対応は必要なく、スタンダードプリコーションの遵守が基本となる。HIVは、HBVやHCVと比較して感染力が弱いため、医療器具の消毒などもHBVのマニュアルに準じて行うことで十分である。針刺しなどの曝露事故の際には、すみやかに抗HIV薬を内服することにより感染率を下げることができる。いざという時に慌てないために、曝露事故時の対応マニュアルなどを各施設で整備しておくことが重要である。(著者抄録)
  • 当院におけるHIV感染者のビタミンDの検討
    遠藤 知之, 藤本 勝也, 南 昭子, 吉田 美穂, 竹村 龍, 渡部 恵子, 坂本 玲子, 武内 阿味, 近藤 健, 橋野 聡, 清水 力, 豊嶋 崇徳  日本エイズ学会誌  17-  (1)  30  -35  2015/02  [Not refereed][Not invited]
     
    HIV感染者におけるビタミンDの充足率を把握し、骨密度低下と因果関係を評価した。方法は著者らの施設へ通院中のHIV患者118例(男性115例、女性3例、年齢24〜73歳、平均年齢43歳)を対象に、血清25水酸化ビタミンD[25(OH)D]を測定、そのうち100例でDXA法による骨塩量測定検査を行った。その結果、1)血清25(OH)Dの平均値は18.5±11.0ng/mlであり、ビタミンD不足(20〜29ng/dl)は24例(20.3%)、ビタミンD欠乏(20ng/dl以下)が79例(67.0%)にみられた。更にビタミンD高度欠乏(10ng/ml以下)は26例(22.0%)にみられ、ビタミンD正常(30ng/ml以上)は15例(12.7%)に過ぎなかった。2)100例におけるDXA法による骨塩定量測定では骨減少症は27例(27.0%)、骨粗鬆症は8例(8%)であった。3)このことからビタミンDの充足度と骨密度には有意な相関は認められなかったが、抗HIV療法を受けている症例では未治療の症例と比較して有意に骨密度が低下していた。4)多くのHIV患者でビタミンDが不足・欠乏していたが、骨密度低下の要因としてはビタミンD欠乏より抗HIV薬の影響が大きいと考えられた。以上より、HIV患者にビスホスフォネートを投与する際にはビタミンDの評価を行い、ビタミンDが低下・欠乏している症例に対するビタミンDの補充も必要と考えられた。
  • TAKAHASHI SHOJIRO, WAKASA KENTARO, IBATA MAKOTO, SHIGEMATSU AKIO, HUJIMOTO KATUYA, ENDO TOMOUKI, NISHIO MITUHUMI, KONDOU TAKESHI, TANAKA JUNJI, HASHINO SATOSHI, ASAKA MASAHIRO, IMAMURA MASAHIRO  無菌生物 = Japanese journal of germfree life and gnotobiology  41-  (2)  106  -107  2011/12/01  [Not refereed][Not invited]
  • SUGITA JUNICHI, MATSUSHITA TAKAE, KASHIWAZAKI HARUHIKO, KOSUGI MIZUHA, TAKAHASHI SHOJIRO, WAKASA KENTARO, SHIRATORI SOUICHI, IBATA MAKOTO, SHONO YUSUKE, SHIGEMATSU AKIO, OBARA MASATO, FUJIMOTO KATSUYA, ENDO TOMOYUKI, NISHIO MITSUFUMI, KONDO TAKESHI, HASHINO SATOSHI, TANAKA JUNJI, ASAKA MASAHIRO, IMAMURA MASAHIRO  Journal of germfree life and gnotobiology  41-  (1)  48  -53  2011/09/01  [Not refereed][Not invited]
  • KANDA Masatoshi, SHIGEMATSU Akio, OKADA Kohei, KASAHARA Ikumi, IWASAKI Junko, YAMAGUCHI Keisuke, ONOZAWA Masahiro, ENDO Tomoyuki, AKIZAWA Koji, ISHIGURO Nobuhiro, HASHINO Satoshi, IMAMURA Masahiro  The Japanese journal of clinical hematology  52-  (3)  118  -123  2011/03/30  [Not refereed][Not invited]
  • SHIGEMATSU AKIO, SUGITA JUNICHI, YAMAMOTO SATOSHI, ONOZAWA MASAHIRO, ENDO TOMOYUKI, KAHATA KAORU, SHIRATORI SOICHI, WAKASA KENTARO, TAKAHATA MUTSUMI, KONDO TAKESHI, TANAKA JUNJI, NISHIO MITSUFUMI, HASHINO SATOSHI, KOIKE TAKAO, ASAKA MASAHIRO, IMAMURA MASAHIRO  Journal of germfree life and gnotobiology  38-  (1)  27  -32  2008/09/01  [Not refereed][Not invited]
  • 乃村 俊史, 阿部 理一郎, 藤本 勝也, 遠藤 知之, 小池 隆夫, 清水 宏  日本皮膚科学会雑誌 = THE JAPANESE JOURNAL OF DERMATOLOGY  115-  (13)  2236  -2238  2005/12  [Not refereed][Not invited]
  • ENDO Tomoyuki, SAWADA Ken-ichi, FUJIMOTO Katsuya, YAMAMOTO Satoshi, TAKASHIMA Hidenori, HASEYAMA Yoshihito, NISHIO Mitsufumi, KOIZUMI Kazuki, KOIKE Takao  Rinsho Ketsueki  41-  (8)  681  -686  2000/08/30  [Not refereed][Not invited]
  • ENDO Tomoyuki, SAWADA Ken-ichi, FUJIMOTO Katsuya, YAMAMOTO Satoshi, TAKASHIMA Hidenori, HASEYAMA Yoshihito, NISHIO Mitsufumi, KOIZUMI Kazuki, KOIKE Takao  Rinsho Ketsueki  41-  (4)  322  -328  2000/04/30  [Not refereed][Not invited]
  • NISHIO Mitsufumi, SAWADA Ken-ichi, KOIZUMI Kazuki, ENDOH Tomoyuki, TAKASHIMA Hidenori, HASHIMOTO Hideaki, HASEYAMA Yoshihito, KATAGIRI Eri, FUKADA Yoshikazu, TAKANO Hina, TARUMI Katashi, YASUKOUCHI Taro, KOIKE Takao  Rinsho Ketsueki  39-  (8)  580  -585  1998/08/30  [Not refereed][Not invited]

Educational Activities

Teaching Experience

  • 医学総論
    開講年度 : 2019
    課程区分 : 博士後期課程
    開講学部 : 医学研究科


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