研究者詳細 - 前田　嘉信

ミネソタレジメンを用いた臍帯血ミニ移植の治療成績:骨髄移植,末梢血幹細胞移植との比較

小林孝一郎, 原嘉孝, 西森久和, 杉山暖子, 久保西四郎, 前田嘉信, 新谷勝美, 品川克至, 池田和真, 谷本光音

日本臨床腫瘍学会学術集会プログラム・抄録集 7th 2009年

Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer.

Hosokawa S, Toyooka S, Fujiwara Y, Tokumo M, Soh J, Takigawa N, Hotta K, Yoshino T, Date H, Tanimoto M, Kiura K

Lung Cancer 66 ( 1 ) 107 - 113 2009年

Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation

Yasushi Hiramatsu, Yoshinobu Maeda, Nobuharu Fujii, Takashi Saito, Yuichiro Nawa, Masamichi Hara, Tomofumi Yano, Shoji Asakura, Kazutaka Sunami, Takayuki Tabayashi, Akira Miyata, Ken-ichi Matsuoka, Katsuji Shinagawa, Kazuma Ikeda, Keitaro Matsuo, Mitsune Tanimoto

INTERNATIONAL JOURNAL OF HEMATOLOGY 88 ( 5 ) 588 - 595 2008年12月

記述言語：英語出版者・発行元：SPRINGER TOKYO

A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, -5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.

DOI： 10.1007/s12185-008-0196-y

Cyclosporine, but Not mTOR Inhibitors, Hampers the Reconstitution of Bone Marrow-Derived Tregs in Long-Term Complete Donor chimeras

Haruko Sugiyama, Yoshinobu Maeda, Hisakazu Nishimori, Koichiro Kobayashi, Miyuki Nishie-Kataoka, Takanori Teshima, Mitsune Tanimoto

BLOOD 112 ( 11 ) 812 - 813 2008年11月

Unrelated Cord Blood Transplantation after Nonmyeloablative Conditioning: Single Institutional Retrospective Comparison with Bone Marrow or Peripheral Blood Stem-Cell Transplants

Kolchiro Kobayashi, Yoshinobu Maeda, Hisakazu Nishimori, Haruko Sugiyama, Kazutoshi Aoyama, Tomoko Kikuchi, Noriko Namba, Shiro Kubonishi, Masami Niiya, Katsuji Shinagawa, Kazuma Ikeda, Mitsune Tanimoto

BLOOD 112 ( 11 ) 687 - 687 2008年11月

Identification of CD123(+) myeloid dendritic cells as an early-stage immature subset with strong tumoristatic potential

Jun Shi, Kazuma Ikeda, Yosinobu Maeda, Katsuji Shinagawa, Aiji Ohtsuka, Hajime Yamamura, Mitsune Tanimoto

CANCER LETTERS 270 ( 1 ) 19 - 29 2008年10月

記述言語：英語出版者・発行元：ELSEVIER IRELAND LTD

CD123 has been identified as a specific surface marker for plasmacytoid dendritic cells (PDCs). However, CD123 has recently been shown to be expressed on freshly isolated or in vitro generated myeloid dendritic cells (MDCs). In this article, we investigated whether the expression of CD123 on monocyte-derived MDCs was related to their function, especially to tumor-inhibiting potential. MDCs were induced from cord blood CD14(+) monocytes with granulocyte-macro phage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days, and then CD123(+) cells were isolated by positive immunomagnetic cell selection. We observed that CD123(+) cells lost monocyte CD14 expression, acquired immature myeloid dendritic cell phenotype and morphology. They exerted more significant endocytosis and less antigen-presenting function than CD123-MDCs which are often referred to as typical MDCs. Meanwhile, CD123(+) MDCs exhibited more significant tumor-inhibiting activity toward hematological tumor cell lines of U937 and Jurkat even at a low effector:target ratio. CD123(+) MDCs expressed higher level of cytoplasmic TNF-alpha-related apoptosis-inducing ligand (TRAIL), but no detectable surface TRAIL and very little soluble TRAIL. Pretreatment with recombinant human TRAIL receptor 2:Fc fusion protein significantly reduced the tumor-inhibiting effect of CD123(+) MDCs, but not of CD123(-) MDCs. Overall, our data demonstrated that CD123(+) MDCs were an early-stage immature DC subset, with a significant tumor-inhibiting activity partially via involvement of enhanced cytoplasmic TRAIL. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.canlet.2008.04.048

治療抵抗性進行期低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植

久保西四郎, 品川克至, 浅田騰, 遠西大輔, 門久幸代, 近藤正太郎, 前田嘉信, 新谷勝美, 池田和真, 谷本光音

臨床血液 49 ( 9 ) 1164 - 1164 2008年9月

Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease 国際誌

Isao Tawara, Yoshinobu Maeda, Yaping Sun, Kathleen P. Lowler, Chen Liu, Tonionii Toubai, Andrew N. J. McKenzie, Pavan Reddy

EXPERIMENTAL HEMATOLOGY 36 ( 8 ) 988 - 996 2008年8月

記述言語：英語出版者・発行元：ELSEVIER SCIENCE INC

The rote of T helper (Th) 1 and Th2 polarization in acute graft-vs-host-disease (GVHD) is unclear. We investigated the role of Th2 cytokine secretion by utilizing donor T cells that cannot make interleukin (IL)-4, IL-5, IL-9, and IL-13 from quadruple cytokine-deficient (Quad-KO) animals, in a well-characterized BALB/c - C57BL/6 model of allogeneic bone marrow transplantation. B6 recipients of BALB/c Quad-KO T cells demonstrated greater clinical severity, target organ damage, and mortality from GVHD than recipients of BALB/c wild-type (WT) T cells. When compared with donor T cells that are deficient in signal transducers and activators of transcription 6 signaling or the signature Th2 cytokine, IL-4, Quad-KO T cells demonstrated greater GVHD mortality. Mechanistic studies demonstrated that Quad-KO T cells demonstrated enhanced T-cell proliferation than WT T cells when stimulated with either allogeneic antigen-presenting cells or with nonspecific stimuli, such as anti-CD3 monoclonal antibody. Quad-KO T cells also secreted greater amounts of Th1 cytokines and IL-17 compared to WT T cells. Deficiency of Th2 cytokines, however, did not alter the allospecific cytotoxic responses, the numbers of immunoregulatory CD4(+)CD25(+) Foxp3(+) T cells or their suppressive functions. Our data thus unequivocally demonstrate that deficiency of the four classical Th2 cytokine enhances T-cell proliferative responses and aggravates GVHD. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

DOI： 10.1016/j.exphem.2008.02.010

Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice 国際誌

Pavan Reddy, Yaping Sun, Tomomi Toubai, Raimon Duran-Struuck, Shawn G. Clouthier, Elizabeth Weisiger, Yoshinobu Maeda, Isao Tawara, Oleg Krijanovski, Erin Gatza, Chen Liu, Chelsea Malter, Paolo Mascagni, Charles A. Dinarello, James L. M. Ferrara

JOURNAL OF CLINICAL INVESTIGATION 118 ( 7 ) 2562 - 2573 2008年7月

記述言語：英語出版者・発行元：AMER SOC CLINICAL INVESTIGATION INC

Histone deacetylase (HDAC) inhibitors are antitumor agents that also have antiinflammatory properties. However the mechanisms of their immunomodulatory functions are not known. We investigated the mechanisms of action of 2 HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and ITF 2357, on mouse DC responses. Pretreatment of DCs with HDAC inhibitors significantly reduced TLR-induced secretion of proinflammatory cytokines, suppressed the expression of CD40 and CD80, and reduced the in vitro and in vivo allo-stimulatory responses induced by the DCs. In addition, injection of DCs treated ex vivo with HDAC inhibitors reduced experimental graft-versus-host disease (GVHD) in a murine allogeneic BM transplantation model. Exposure of DCs to HDAC inhibitors increased expression of indoleamine 2.3-dioxygenase (IDO), a suppressor of DC function. Blockade of IDO in WT DCs with siRNA and with DCs from IDO-deficient animals caused substantial reversal of HDAC inhibition-induced in vitro suppression of DC-stimulated responses. Direct injection of HDAC inhibitors early after allogeneic BM transplantation to chimeric animals whose BM-derived cells lacked IDO failed to protect from GVHD, demonstrating an in vivo functional role for IDO. Together, these data show that HDAC inhibitors regulate multiple DC functions through the induction of IDO and suggest that they may represent a novel class of agents to treat immune-mediated diseases.

DOI： 10.1172/JCI34712

同種造血幹細胞移植後再発・生着不全に対する再移植

小林孝一郎, 近藤正太郎, 片岡美由紀, 原嘉孝, 西森久和, 杉山暖子, 菊池智子, 久保西四郎, 前田嘉信, 新谷勝美, 品川克至, 池田和真, 谷本光音

日本臨床腫瘍学会学術集会プログラム・抄録集 6th 2008年

Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease

Yoshinobu Maeda, Isao Tawara, Takanori Teshima, Chen Liu, Daigo Hashimoto, Ken-ichi Matsuoka, Mitsune Tanimoto, Pavan Reddy

EXPERIMENTAL HEMATOLOGY 35 ( 2 ) 274 - 286 2007年2月

記述言語：英語出版者・発行元：ELSEVIER SCIENCE INC

Objective. T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naive T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known.
Methods. We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naive T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT).
Results. Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naive T cells. Compared to naive donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44(hi) "memory" phenotype T cells and not the CD4(+)CD25(+) T cell subset to be critical for the reduction in GVHD.
Conclusions. These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.

DOI： 10.1016/j.exphem.2006.10.010

Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease 国際誌

Yoshinobu Maeda, Isao Tawara, Takanori Teshima, Chen Liu, Daigo Hashimoto, Ken-ichi Matsuoka, Mitsune Tanimoto, Pavan Reddy

EXPERIMENTAL HEMATOLOGY 35 ( 2 ) 274 - 286 2007年2月

記述言語：英語出版者・発行元：ELSEVIER SCIENCE INC

DOI： 10.1016/j.exphem.2006.10.010

Predominant infiltration of monocytes in chronic graft-versus-host disease

Noriko Namba, Katsuii Shinagawa, Nobuharu Fujii, Yoshinobu Maeda, Fumihiko Ishimaru, Kazurna Ikeda, Toshimitsu Matsui, Mitsune Tanimoto, Yoshio Katayama

TRANSPLANTATION 83 ( 2 ) 220 - 224 2007年1月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Pathogenesis of chronic graft-versus-host disease (cGVHD) is largely unknown. It is important to determine the responsible cell types and the factors that play roles to recruit these cells into sites of disease. We examined whether monocytes and chemokine fractalkine/receptor CX3CR1 axis might be involved. We found that the absolute number of CX3CR1 + monocytes in the blood was significantly decreased in patients with severe cGVHD. Immunohistochemical staining revealed the extensive infiltration of CD 14 + cells as well as strong expression of fractalkine in the cGVHD skin. The number of infiltrated CD14+ cells on the margin of fractatkine+ epidermis was larger in cGVHD skin compared to that of acute graft-versus-host disease, whereas no difference was observed in CD3 + T cells. These results suggest that CX3CR1+ monocytes may be recruited from the circulation to the fractalkine + epidermis in cGVHD, and highlight these cells and this chemokine/receptor axis as additional targets for cGVHD therapy.

DOI： 10.1097/01.tp.0000245080.71722.87

Predominant infiltration of monocytes in chronic graft-versus-host disease 国際誌

Noriko Namba, Katsuii Shinagawa, Nobuharu Fujii, Yoshinobu Maeda, Fumihiko Ishimaru, Kazurna Ikeda, Toshimitsu Matsui, Mitsune Tanimoto, Yoshio Katayama

TRANSPLANTATION 83 ( 2 ) 220 - 224 2007年1月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

DOI： 10.1097/01.tp.0000245080.71722.87