研究者詳細 - 瀧澤　淳

Anti-tumor cytotoxicity of gamma delta T cells expanded from peripheral blood cells of patients with myeloma and lymphoma 査読

Anri Saitoh, Miwako Narita, Norihiro Watanabe, Nozomi Tochiki, Noriyuki Satoh, Jun Takizawa, Tatsuo Furukawa, Ken Toba, Yoshifusa Aizawa, Shohji Shinada, Masuhiro Takahashi

MEDICAL ONCOLOGY 25 ( 2 ) 137 - 147 2008年6月

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

In order to establish an efficient gamma delta T cell-mediated immunotherapy for hematological malignancies, we attempted to evaluate cytotoxicity against tumor cells by gamma delta T cells, which were generated from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and a low dose of IL-2. Although gamma delta T cells were expanded in patients with myeloma and lymphoma as well as normal persons, the amplification rates of gamma delta T cells before and after culturing varied from patient to patient in myeloma and lymphoma. gamma delta T cells generated in patients with myeloma and lymphoma showed a potent cytotoxic ability against myeloma/lymphoma cell lines as shown in gamma delta T cells generated in normal subjects. In addition, gamma delta T cells generated in a patient with myeloma showed a cytotoxic ability against self myeloma cells freshly prepared from bone marrow. However, the same gamma delta T cells were demonstrated to be non-cytotoxic to normal cells of the patient. These data demonstrated that gamma delta T cells, which could be expanded in vitro from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and IL-2, possess a sufficient cytotoxic ability against tumor cells. These findings suggested that in vitro generated patients' gamma delta T cells could be applied to gamma delta T cell-mediated immunotherapy for hematological malignancies.

DOI： 10.1007/s12032-007-9004-4

Successful treatment of adult T-cell leukemia with unrelated cord blood transplantation 査読

Jun Takizawa, Sadao Aoki, Tori Kurasaki, Masutaka Higashimura, Keiichiro Honma, Toshiki Kitajima, Akihito Momoi, Hidenobu Takahashi, Naoya Nakamura, Tatsuo Furukawa, Yoshifusa Aizawal

AMERICAN JOURNAL OF HEMATOLOGY 82 ( 12 ) 1113 - 1115 2007年12月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

This study reports the first well-documented case of adult T-cell leukemia (ATL) successfully treated with unrelated cord blood transplantation (UCBT). A 49-year-old woman was diagnosed with acute-type of ATL. Chemotherapy induced complete remission, but the human T-cell leukemia virus type 1 (HTLV-1) proviral load was detected in mononuclear cells of her peripheral blood. The patient received UCBT with a conditioning regimen consisting of total body irradiation, cytarabine, and cyclophosphamide. She remains in remission 30 months after UCBT and the HTLV-1 proviral load has fallen to undetectable levels. This result suggests that UCBT should be a therapeutic option for ATL patients who do not have suitable donors and those who urgently require treatment. Am. J. Hematol. 82:1113-1115, 2007. (c) 2007 Wiley-Liss, Inc.

DOI： 10.1002/ajh.21042

Enhancement of anti-tumor cytotoxicity of expanded gammadelta T Cells by stimulation with monocyte-derived dendritic cells. 査読

Saito A, Narita M, Yokoyama A, Watanabe N, Tochiki N, Satoh N, Takizawa J, Furukawa T, Toba K, Fuse I, Aizawa Y, Shinada S, Takahashi M

J Clin Exp Hematop. 47 ( 2 ) 61 - 72 2007年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：The Japanese Society for Lymphoreticular Tissue Research

In order to establish the method of generating powerful γδ T cells for anti-tumor immunotherapy, we investigated the effects of monocyte-derived dendritic cells (mo-DCs) on anti-tumor cytotoxicity of expanded γδ T cells. Activation of γδ T cells co-cultured for 2-3 days with immature or mature mo-DCs was evaluated by CD69 expression and anti-tumor cytotoxicity using two assays : the 5- (and 6-) carboxyfluorescein diacetate, succinimidyl ester-based cytotoxicity assay and the calcein-AM-based Terascan assay. γδ T cells were used as effector cells and myeloma cell line (RPMI8226) or chronic myelogenous leukemia blastic crisis cell line (C2F8) were used as target cells. CD69 expression on γδ T cells was enhanced by co-culture with both immature and mature mo-DCs in a cell-number-dependent fashion. CD69 expression was enhanced after addition of mo-DCs of either autologous or allogeneic origin. Activation of γδ T cells with mo-DCs enhanced anti-tumor cytotoxicity of γδ T cells against RPMI8226 and C2F8 in an effector-to-target ratio-dependent manner. Activation of γδ T cells by mo-DCs was associated with the enhancement of anti-tumor cytotoxicity of γδ T cells. Potent γδ T cells activated by mo-DCs were considered to be applicable to an efficient γδ T cell-mediated immunotherapy for tumors. [J Clin Exp Hematopathol 47(2) : 61-72, 2007]

DOI： 10.3960/jslrt.47.61

CiNii Article

CiNii Books

その他リンク： http://search.jamas.or.jp/link/ui/2008186007

Identification of an overexpressed gene, HSPA4L, the product of which can provoke prevalent humoral immune responses in leukemia patients 査読

Hidenobu Takahashi, Tatsuo Furukawa, Toshio Yano, Naoko Sato, Jun Takizawa, Tori Kurasaki, Takashi Abe, Miwako Narita, Masayoshi Masuko, Satoru Koyama, Ken Toba, Masuhiro Takahashi, Yoshifusa Aizawa

EXPERIMENTAL HEMATOLOGY 35 ( 7 ) 1091 - 1099 2007年7月

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

Objective. To identify leukemia-associated antigens, we applied the serological identification of antigens by the recombinant expression cloning (SEREX) method to a chronic myelogenous leukemia (CML) patient who achieved a cytogenetic response to interferon-alpha.
Materials and Methods. Immunoscreening of the cDNA library was performed with sera from a CML patient. Two isolated antigens were used to evaluate the expression pattern using Northern blot analysis and quantitative reverse transcriptase polymerase chain reaction. Western blotting and enzyme-linked immunosorbent assay were also performed for serological analysis.
Results. We identified 14 positive clones, representing five different antigens. Of these, two genes were further validated. One (clone 70) was the human polyribonucleotide nucleotidyltransferase 1 (PNPT1), which is the type I interferon (alpha/beta-responsive gene). The mRNA of clone 70 was ubiquitously expressed in normal human tissues. The other gene (clone 57) was the heat shock 70-kDa protein 4-like (HSPA4L), which is a member of the heat shock protein 110 family, whose mRNA is strongly expressed in normal human testis and overexpressed in leukemia cells. Seroactivity against HSPA4L was detected in 6 of 9 acute myeloid leukemia patients, 4 of 10 acute lymphoblastic leukemia patients, 9 of 11 CML patients, and none of 10 healthy volunteers. Leukemia patients had higher titer of the antibodies against the protein than healthy volunteers.
Conclusions. These results suggest that HSPA4L, a member of heat shock protein, is highly expressed by leukemia cells, and elicit humoral immune responses in leukemia patients, and it might be a potential target for antileukemia therapy and an antigen-specific immunotherapy for leukemia.

DOI： 10.1016/j.exphem.2007.03.015

Plasma brain natriuretic peptide during myeloablative stem cell transplantation. 査読

Masuko M, Ito M, Kurasaki T, Yano T, Takizawa J, Toba K, Aoki S, Fuse I, Kodama M, Furukawa T, Aizawa Y

Internal medicine (Tokyo, Japan) 46 ( 9 ) 551 - 555 2007年

記述言語：英語出版者・発行元：The Japanese Society of Internal Medicine

Objective: Cardiovascular complication is one of the serious complications in stem cell transplantation (SCT). We measured plasma brain natriuretic peptide (BNP) concentrations in patients who received SCT to evaluate possible cardiac toxicity of the regimens employed in SCT. Patients: Ten patients with allogeneic SCT and 5 patients with autologous SCT using myeloablative conditioning regimens were enrolled. The preparative chemotherapy for 8 patients with allogeneic SCT included cyclophosphamide (60 mg/kg i.v. for 2 days) and other drugs and that for autologous SCT included cyclophosphamide (50 mg/kg for 2 days) and other drugs. Total body irradiation (TBI) was employed only in the patients who received allogeneic SCT. Method: Plasma BNP was measured using a radioimmunoassay for human BNP before and after SCT. Results: In 13 of 15 patients, BNP levels were elevated after SCT. In patients who received a total body irradiation (TBI) of 13.2 Gy, BNP levels were higher than those without irradiation (p=0.01). The BNP level reached a peak within 6 months after SCT in most patients and fell thereafter. But 7 of the 15 patients (46.7%) had an abnormally high level of plasma BNP even after 6 months of SCT which suggests subclinical myocardial damage. Conclusion: A rise in plasma BNP was frequently observed after SCT, and may be considered to represent cardiac damage caused by the preparative chemotherapy and/or total body irradiation. Since a rise was noted 6 months after SCT, long-term evaluation of cardiac function is important.

DOI： 10.2169/internalmedicine.46.6188

CiNii Article

その他リンク： http://search.jamas.or.jp/link/ui/2007315596

Expression of BAFF-R (BR3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody 査読

N Nakamura, H Hase, D Sakurai, S Yoshida, M Abe, N Tsukada, J Takizawa, S Aoki, M Kojima, S Nakamura, T Kobata

VIRCHOWS ARCHIV 447 ( 1 ) 53 - 60 2005年7月

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

BAFF-receptor (BAFF-R) is required for the successful maturation and survival of B-cells. We developed an anti-human BAFF-R monoclonal antibody (mAb), 8A7. The reactivity of 8A7 in normal and neoplastic tissue was examined by performing immunohistochemistry on paraffin-embedded sections. 8A7 reacted with lymphocytes in the mantle and marginal zones, but not with lymphocytes in the interfollicular area. Lymphocytes in the germinal centers were found to be negative or occasionally weakly positive for 8A7. BAFF-R expression was found only in B-cell lymphoma (44/80, positive cases/examined cases): B-lymphoblastic lymphoma 0/3, B-chronic lymphocytic leukemia/small lymphocytic lymphoma 4/4, mantle cell lymphoma 9/11, follicular lymphoma 10/14, diffuse large B-cell lymphoma (DLBCL) 11/25, marginal zone B-cell lymphoma 8/10, lymphoplasmacytic lymphoma 2/2, plasma cell myeloma 0/2, and Burkitt lymphoma 0/9, but not in T/NK cell lymphomas (0/19) or Hodgkin lymphoma (0/10). BAFF-R was expressed in most low-grade B-cell neoplasms and a small number of DLBCL, suggesting that BAFF-R may play an important role in the proliferation of neoplastic lymphoid cells. Thus, the mAb is very useful for further understanding of both healthy B-cell biology and its pathogenic neoplasms.

DOI： 10.1007/s00428-005-1275-6

IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy 査読

G Hatzivassiliou, Miller, I, J Takizawa, N Palanisamy, PH Rao, S Iida, S Tagawa, M Taniwaki, J Russo, A Neri, G Cattoretti, R Clynes, C Mendelsohn, RSK Chaganti, R Dalla-Favera

IMMUNITY 14 ( 3 ) 277 - 289 2001年3月

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

Abnormalities of chromosome 1q21 are common in B cell malignancies, but their target genes are largely unknown. By cloning the breakpoints of a (1;14) (q21;q32) chromosomal translocation in a myeloma cell line, we have identified two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to the Fc and inhibitory receptor families. Both genes are selectively expressed in mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal zone B cells, and immunoblasts. As a result of the t(1;14), IRTA1 is fused to the immunoglobulin C alpha domain to produce a chimeric IRTA1/C alpha fusion protein. In tumor cell lines with 1q21 abnormalities, IRTA2 expression is deregulated. Thus, IRTA1 and IRTA2 are novel immunoreceptors implicated in B cell development and lymphomagenesis.

DOI： 10.1016/S1074-7613(01)00109-1

5q- syndrome presenting chronic myeloproliferative disorders-like manifestation: A case report 査読

Hidenobu Takahashi, Tatsuo Furukawa, Shigeo Hashimoto, Naoko Kanazawa, Naoaki Satoh, Noriatsu Suzuki, Jun Takizawa, Yumiko Uesugi, Masuhiro Takahashi, Yoshifusa Aizawa, Tadashi Koike

American Journal of Hematology 64 ( 2 ) 120 - 123 2000年

記述言語：英語掲載種別：研究論文（学術雑誌）

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 x 109/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of 'mixed myelodysplastic and myeloproliferative syndromes' and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/(SICI)1096-8652(200006)64:2<120::AID-AJH9>3.0.CO;2-M

Scopus

The TCL1 oncogene is not overexpressed in patients with adult T cell leukemia 査読

J Takizawa, M Seto

LEUKEMIA 13 ( 2 ) 314 - 314 1999年2月

Expression of the TCL1 gene at 14q32 in B-cell malignancies but not in adult T-cell leukemia 査読

J Takizawa, R Suzuki, H Kuroda, A Utsunomiya, Y Kagami, T Joh, Y Aizawa, R Ueda, M Seto

JAPANESE JOURNAL OF CANCER RESEARCH 89 ( 7 ) 712 - 718 1998年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI IRELAND LTD

The TCL1 gene was recently cloned as a candidate target within the 14q32.1 breakpoint cluster region observed in T-cell malignancies. We examined the TCL1 gene expression in 21 patients with adult T-cell leukemia (ATL) and 5 cell Lines, because ATL is reported to have frequent chromosome 14 band (q32 aberrations, However, 20 of the ATL patients and all 5 cell lines lacked any TCL1 expression on northern blot analysis, and TCL1 transcripts were only very faintly detected in the remaining one patient, Expansion of our analysis to include other types of hematopoietic malignancies revealed strong expression of the TCL1 gene in almost all tumor cells of B-cell lineage except myelomas. However no TCL1 signals were encountered in cells of T-cell or myeloid lineages. In normal human tissues TCL1 was found to be expressed in the spleen. lymph nodes and B-lymphocytes of peripheral blood. These results indicate that TCL1 is not a major target gene for ATL, but that it may play a role in B-cell differentiation and proliferation.

DOI： 10.1111/j.1349-7006.1998.tb03275.x

Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation 査読

Tatsuroh Joh, Yoshitoyo Kagami, Kazuhito Yamamoto, Tatsuya Segawa, Jun Takizawa, Toshitada Takahashi, Ryuzo Ueda, Masao Seto

Oncogene 13 ( 9 ) 1945 - 1953 1996年

記述言語：英語掲載種別：研究論文（学術雑誌）

11q23 chromosome aberrations are frequently observed in infantile as well as therapy-related leukemias. The target gene at 11q23, MLL, is disrupted by the translocation and becomes fused to various translocation partner genes such as AF4/FEL, LTG9/AF9 and LTG19/ENL. The resulting chimeric mRNAs are fused in frame and have been predicted to encode leukemia-specific chimeric proteins. In the present study, we raised antibodies against MLL, LTG9 and LTG19 and demonstrated that MLL and chimeric MLL-LTG9 and MLL-LTG19 products are synthesized in vivo and are localized in the nuclei, using immunofluorescence and cell fractionation studies. The truncated N-terminal portion of the MLL product common to the various types of 11q23 translocation was also localized in the nuclei in a similar fashion. Murine 32Dc13 cells stably expressing the truncated N-terminal MLL protein exhibited an inhibition of differentiation and a growth advantage following stimulation by granulocyte-colony stimulating factor, although the IL-3 dependency was not significantly changed in comparison to the parental cells. These results suggest that the N-terminal portion common to various MLL-chimeric products plays an important role in leukemogenesis.

Scopus

Fanconi貧血と思われる再生不良性貧血に続発した急性骨髄性白血病に親子間同種骨髄移植を施行した1症例査読

瀧澤淳, 岸賢治, 森山美昭, 橋本誠雄, 後藤隆夫, 樋口渉, 和田研, 成田美和子, 青木定夫, 高橋益広, 小池正, 柴田昭

臨床血液 36 ( 6 ) 615 - 620 1995年6月

担当区分：筆頭著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本血液学会

症例は19歳，男性。生後1カ月より貧血を指摘され，低身長，右母指形成不全，皮膚色素沈着，精神発達遅延など多発奇形を合併しており，Fanconi貧血(FA)が疑われ経過観察されてきた。1993年1月より，汎血球減少が著明となり，頻回の輸血が必要となったため，8月31日当科入院となった。入院時骨髄穿刺では，骨髄は有核細胞数1.1×104/μlと低形成であったが，芽球42.0%, 前骨髄球9.6%を認め，AML (M2)へ移行したものと判断した。少量Ara-C療法で寛解は得られず，HLA完全一致，MLC陰性の父親をdonorとして，10月15日同種骨髄移植を施行した。移植前処置はcyclophosphamideを用いず，Ara-Cとetoposideの大量投与とTBI (12Gy)を併用したが，重篤なregimen related toxicityは認めず，骨髄生着が得られた。急性GVHD予防はciclosporin Aとmethotrexateを用い，GVHDは認められなかった。白血病に移行したFAに対するBMT成功例は少なく，文献的考察を含め報告する。

DOI： 10.11406/rinketsu.36.615

CiNii Article

CiNii Books