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Publications (6)5.58 Total impact

  • Article: The potential of patients' peripheral blood mononuclear cells to differentiate into dendritic cells after hematopoietic stem cell transplantation.
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    ABSTRACT: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological disorders, there is persistent immunosuppression in both allogeneic and autologous HSCT. Dendritic cells (DCs) play key roles in the immune system. This study investigated whether the DC progenitor cells within patients' peripheral blood after HSCT have the potential to differentiate into DCs. Twenty-eight patients were included in this study, and peripheral blood samples were basically taken before starting the conditioning regimen, on the day of transplantation (day 0), and on days +14, +28, +42, +70 and +170 after transplantation. Immature DCs (iDCs) were induced from adherent mononuclear cells by using recombinant human granulocyte-macrophage colony-stimulating factor plus interleukin-4. The iDCs expressed cell surface antigens such as CD40 and HLA-DR, and they had phagocytotic activity, thus showing the characteristics of iDCs. The induction of iDCs was possible from day +14 after HSCT. However, there were differences between allogeneic and autologous HSCT in the expression of CCR5 in iDCs at day +14 after transplantation. Furthermore, the up-regulation of maturation-related antigens by maturation stimuli was higher after HSCT compared with before HSCT. We demonstrated that patients' peripheral blood mononuclear cells have the potential to differentiate into DCs beginning on day +14 after HSCT, although some differences exist between allogeneic and autologous HSCT and between before and after HSCT.
    Life sciences 12/2011; 89(25-26):946-55. · 2.56 Impact Factor
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    Article: Monitoring twenty-six chronic myeloid leukemia patients by BCR-ABL mRNA level in bone marrow:a single hospital experience.
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    ABSTRACT: Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300 mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300 mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML.
    Acta medica Okayama 10/2011; 65(5):335-42. · 0.84 Impact Factor
  • Article: Comparison of long-term clinical outcomes of CHOP chemotherapy between Japanese patients with nodal peripheral T-cell lymphomas and those with diffuse large B-cell lymphoma in the study group of the Tohoku Hematology Forum.
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    ABSTRACT: To clarify the clinical outcome of peripheral T-cell lymphomas (PTCLs), we conducted a retrospective review comparing the outcomes of patients with PTCL (nodal peripheral T-cell lymphoma, unspecified, n=34 ; angioimmunoblastic T-cell lymphoma, n=12) to those with diffuse large B-cell lymphoma (DLBCL, n=48). All patients received CHOP-based chemotherapy without rituximab. PTCL patients presented at a more advanced clinical stage (91% vs. 65%, P<0.002) with a poorer performance status (26% vs. 17%, P<0.002) than DLBCL patients. The complete response rate among PTCL patients was significantly lower than among DLBCL patients (39% vs. 67%, P<0.008), as was the 3-year overall survival rate (26% vs. 50%, P=0.005), and Cox multivariate analysis revealed immunophenotype, performance status, and extranodal site involved to be significantly associated with shorter overall survival (P=0.045, P=0.007, and P=0.034, respectively). Our findings suggest that PTCL patients tend to have a poor prognosis associated with several initial risk factors. Moreover, the T-cell phenotype itself appears to have a significant impact on overall survival. Thus, standard CHOP chemotherapy may be inadequate for PTCLs, especially in patients with high-risk factors. The development of newly stratified therapies for the treatment of PTCLs would be highly desirable.
    Journal of Clinical and Experimental Hematopathology 01/2011; 51(1):29-35.
  • Article: WT1 mRNA level in peripheral blood is a sensitive biomarker for monitoring minimal residual disease in acute myeloid leukemia.
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    ABSTRACT: The Wilms' tumor gene 1 (WT1) encodes a transcription factor that is involved in normal cellular development and cell survival. WT1 mRNA is overexpressed in the minimal residual disease (MRD) of patients with hematopoietic malignancy patients, particularly acute myeloid leukemia (AML). MRD represents the condition with the low levels of leukemia cells in the bone marrow and is known as a sign of recurrence. In hematopoietic malignancies, definition of remission is based on the lack of MRD at submicroscopic level. Between December 2005 and June 2008, we started to measure WT1 mRNA levels in the peripheral blood (PB) from patients by quantitative real-time PCR in Aomori Prefectural Central Hospital. Three hundreds and eight samples from 95 patients were evaluated. The patients included AML (55 patients), acute lymphoblastic leukemia (11), myelodysplastic syndrome (20), malignant lymphoma (5), chronic myeloid leukemia (1), prostatic carcinoma (1), and leukopenia (2). Among the 55 AML patients, 21 patients were pretreated with remission induction therapy. In the clinical course of 21 patients, timely therapeutic approaches could be started for relapse by the early detection of WT1 mRNA overexpression before the morphological findings were apparent. Monitoring WT1 mRNA is helpful to identify patients at high-risk relapse. High overall survival rate (71.2%, 15/21, median: 24.6 months, range 1.1-35.6 months) was achieved in 3 years. The overall survival rate of 34 post-treatment patients was 61.7% (median: 23.5 months, range 0.13-126.5 months after treatment start). In conclusion, the WT1 mRNA level is a sensitive biomarker for monitoring MRD.
    The Tohoku Journal of Experimental Medicine 10/2009; 219(2):169-76. · 1.24 Impact Factor
  • Article: [Long-term complete remission after single therapy with gemtuzumab ozogamicin for refractory AML in an elderly patient].
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    ABSTRACT: Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, that is rapidly internalized after binding to CD33. This is followed by intracellular release of calicheamicin, which induces double-stranded DNA breaks, cell cycle arrest, and apoptosis. So GO is a more selective agent for acute myeloid leukemia (AML), because the CD33 antigen is expressed on AML, while it is not expressed on normal hematopoietic stem cells and nonhematopoietic tissues. However, some studies indicated that this agent showed resistance to refractory AML cells via various mechanisms, and that there were no potent effects. In this study, we report a 76-year-old female with recurrent AML who responded to single therapy with GO, achieving complete remission for more than 1 year after the start of administration, although additional remission induction was impossible. The response to GO can be stratified with reference to the response to conventional chemotherapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 12/2007; 34(11):1881-3.
  • Article: Slowly progressive type 1 diabetes mellitus associated with vitiligo vulgaris, chronic thyroiditis, and pernicious anemia.
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    ABSTRACT: A 81-year-old woman was diagnosed as having diabetes mellitus (DM) at 58 years of age. She started insulin therapy the following year, but her blood sugar levels were poorly controlled. At the age of 75, she tested positive for the anti-GAD antibody (7.8 U/ml) and was diagnosed as having slowly progressive type 1 DM (SPIDDM), as well as vitiligo vulgaris. At 78 years of age, chronic thyroiditis was diagnosed after positive tests for anti-thyroid peroxidase antibody and anti-thyroglobulin antibody. At the age of 81, general fatigue and jaundice appeared concomitantly with severe anemia, with Hb levels at 5.2 g/dl. Low serum vitamin B12 levels and the finding of erythroblastic hyperplasia with megaloblasts in bone marrow led to the diagnosis of pernicious anemia. Anemia was alleviated by intramuscular injections of vitamin B12. The patient developed chronic thyroiditis, vitiligo vulgaris, and pernicious anemia concomitantly with SPIDDM, and was diagnosed as having polyglandular autoimmune syndrome type III. Attention should be paid to these potentially associated autoimmune diseases in daily practice during the follow-up of SPIDDM patients.
    Internal Medicine 01/2005; 43(12):1183-5. · 0.94 Impact Factor