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Tomoyasu Suzuki,
Ken Toba,
Kiminori Kato,
Takuya Ozawa,
Masutaka Higasimura, Toshiki Kitajima,
Hirotaka Oda,
Keiichi Tsuchida,
Naohisa Tomosugi,
Hideki Saitoh,
Yoshifusa Aizawa
International journal of cardiology 10/2012; · 7.08 Impact Factor
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Miwako Narita,
Masayoshi Masuko,
Tohri Kurasaki, Toshiki Kitajima,
Shoko Takenouchi,
Anri Saitoh,
Norihiro Watanabe,
Tatsuo Furukawa,
Ken Toba,
Ichiro Fuse,
Yoshifusa Aizawa,
Manabu Kawakami,
Yoshihiro Oka,
Haruo Sugiyama,
Masuhiro Takahashi
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ABSTRACT: Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9 mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer(+)CD8(+) CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 10(6) CD8(+) T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.
International journal of medical sciences 01/2010; 7(2):72-81. · 2.24 Impact Factor
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ABSTRACT: Philadelphia (Ph) chromosome as a result of t (9; 22) (q34; q11) is observed in more than 90% of chromic myeloid leukemia (CML) patients. Cases in which the typical Ph chromosome is not visible at the karyotype level comprise 5-10% of CML patients. CML cases with fusion transcripts such as e13a3 in which ABL exon 3 rather than exon 2 has fused to BCR are very rare. Such reported cases with the e13a3 transcript show the Ph chromosome on karyotype analysis. We reported an atypical karyotype CML patient with the e13a3 BCR-ABL transcript caused by complex translocation. Fluorescence in situ hybridization (FISH) analysis of the metaphase led to a precise cytogenetical characterization. The patient showed favorable response to imatinib, and achieved major molecular responses.
International journal of hematology 07/2009; 90(2):230-4. · 1.17 Impact Factor
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Takashi Abe, Toshiki Kitajima,
Keiichiro Honma,
Tori Kurasaki,
Kiyoshi Okazuka,
Yasuhiko Shibasaki,
Akihito Momoi,
Takashi Kuroha,
Masayoshi Masuko,
Kumiko Yagisawa,
Tatsuo Furukawa,
Ken Toba,
Yoshifusa Aizawa
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ABSTRACT: A 26-year-old woman with acute lymphoblastic leukemia (ALL) relapsed three times after HLA-matched related bone marrow transplantation. Initially, ALL relapsed in the central nervous system (CNS) 1 year after transplantation. Then, ALL relapsed as a single bone tumor involving the CNS and pelvis 4 years after transplantation. Finally, multiple bone tumors in the pelvis and lumbar bones were found as well as spread to the bone marrow 5 years after transplantation. Bone marrow aspiration also showed ALL relapse. Flow cytometry analyses detected CD20-positive cells in the bone tumor. Though the initial bone tumor was resistant to hyper CVAD, radiation was effective and this patient achieved complete remission. At that time, the total radiation dose had already reached the upper limit. After the third relapse, bone marrow achieved complete remission with the administration of pirarubicin, vincristine, prednisolone, and L-asparaginase (arranged DVP-L), though this combination chemotherapy itself was not effective in multiple bone tumors. Thereafter, arranged DVP-L plus rituximab was administered, which resulted in significant tumor reduction. Biweekly rituximab administration as maintenance therapy has completely prevented the regrowth of bone tumors. Rituximab for relapsed CD20-positive ALL patients after stem cell transplantation could be beneficial.
[Rinshō ketsueki] The Japanese journal of clinical hematology 12/2008; 49(11):1556-61.
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Yashiro Makiyama,
Ken Toba,
Kiminori Kato,
Satoru Hirono,
Takuya Ozawa,
Takashi Saigawa,
Shiro Minagawa,
Manabu Isoda,
Fuyuki Asami,
Noboru Ikarashi,
Masato Oda,
Masato Moriyama,
Masutaka Higashimura, Toshiki Kitajima,
Keita Otaki,
Yoshifusa Aizawa
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ABSTRACT: Restenosis is a major problem in percutaneous catheter intervention (PCI) for coronary artery stenosis in patients with acute myocardial infarction. Coronary restenosis arises from intimal hyperplasia, i.e., hyperplasia of the vascular smooth muscle cells (SMCs) caused by endothelial cell (EC) damage due to PCI. Drug eluting stent (DES), a novel stent coated with a cell-growth inhibitor, such as rapamycin, has been utilized to block SMC proliferation, but DES also blocks EC repair and thus requires the administration of anti-platelets for a long time to prevent thrombus formation after PCI. Moreover, insufficient prevention of platelet aggregation sometimes induces restenosis after PCI. One of the signal transduction inhibitors, imatinib mesilate, blocks tyrosine kinase activity of platelet-derived growth factor receptor (PDGFR), and therefore it may block the development of neointima through growth inhibition of SMCs without the obstructive effect on EC-repair. We therefore studied the effects of imatinib on neointimal hyperplasia in a balloon injury model of rat carotid arteries. Rats were orally administered with imatinib for 14 days after balloon injury, and sacrificed to analyze the neointimal formation. Intimal hyperplasia was inhibited by imatinib in a dose-dependent manner. Therefore imatinib presumably obstructed the growth of SMCs via interception on growth-signaling of PDGFR. The administration of imatinib after coronary stenting or the use of an imatinib-eluting stent may further reduce the risk of restenosis in patients.
The Tohoku Journal of Experimental Medicine 09/2008; 215(4):299-306. · 1.24 Impact Factor
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Jun Takizawa,
Sadao Aoki,
Tori Kurasaki,
Masutaka Higashimura,
Keiichiro Honma, Toshiki Kitajima,
Akihito Momoi,
Hidenobu Takahashi,
Naoya Nakamura,
Tatsuo Furukawa,
Yoshifusa Aizawa
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ABSTRACT: 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.
American Journal of Hematology 01/2008; 82(12):1113-5. · 4.67 Impact Factor
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Masato Oda,
Kiminori Kato,
Ken Toba,
Keita Otaki, Toshiki Kitajima,
Noboru Ikarashi,
Takao Yanagawa,
Masutaka Higashimura,
Fuyuki Asami,
Manabu Isoda,
Takuya Ozawa,
Masato Moriyama,
Satoru Hirono,
Yuji Okura,
Haruo Hanawa,
Makoto Kodama,
Yoshifusa Aizawa
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ABSTRACT: Autologous bone marrow implantation (BMI) is effective to treat critical limb ischemia, but the long-term prognosis is not clear. The outcome of BMI treatment for ischemic legs was investigated related to the clinical background of the patient, and short-term effects of BMI. The end event was defined as unexpected lower limb amputation.
This study included 21 consecutive patients (mean age 60.0 +/- 13.6 years) with peripheral arterial disease who underwent BMI between December 2001 and March 2005. Twelve patients had arteriosclerosis obliterans (ASO), 5 had Buerger disease (thromboangiitis obliterans), 3 had thromboembolism, and 1 had hypereosinophilic syndrome. The patients with ASO had severe complications such as diabetes and hyperlipidemia. The total number of transplanted CD34-positive cells, ankle-brachial pressure index (ABI), and tissue oxygen pressure (TcO2) were lower in ASO patients than non-ASO patients. Significant risk factors for the event were diagnosis of ASO and low TcO2 (< 30 mmHg) according to the Kaplan-Meier survival curve and log rank test. All 6 patients who required limb amputation had ASO simultaneously with low TcO2 (6 of 9, 67%). In contrast, there was no correlation between the end event and short-term effect of BMI such as improvements in ABI and TcO2.
Treatment with BMI could not save legs in some patients with ASO associated with severe leg ischemia.
Journal of Cardiology 10/2007; 50(4):235-42. · 1.28 Impact Factor
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Takuya Ozawa,
Kiminori Kato,
Ken Toba,
Masato Oda,
Manabu Isoda,
Fuyuki Asami,
Noboru Ikarashi,
Takao Yanagawa,
Masato Moriyama,
Masutaka Higashimura, Toshiki Kitajima,
Keita Otaki,
Tsugumi Takayama,
Satoru Hirono,
Yuji Okura,
Haruo Hanawa,
Makoto Kodama,
Yoshifusa Aizawa
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ABSTRACT: Bone marrow implantation (BMI) has been utilized for the treatment of limb ischemia, however, serum markers have not yet been reported to express the degree of limb ischemia. We analyzed the serum levels of several cytokines including erythropoietin (EPO) in the treated legs and the contralateral ones in 11 patients with limb ischemia treated with BMI. The EPO level in the pre-treated legs in the 5 patients with arteriosclerosis obliterans revealed a good correlation with ankle-brachial pressure index. The EPO level, but not the levels of TNF-alpha, VEGF, and bFGF in the pre-treated legs was significantly higher than that in the contralateral legs in the 11 patients, and the EPO level decreased in 4 weeks after BMI. The serum EPO level may express the degree of limb ischemia presumably through the reactive production of EPO in ischemic tissue.
International journal of cardiology 08/2007; 130(1):106-8. · 7.08 Impact Factor
