Yasunobu Abe

National Cancer Center, Japan, Edo, Tokyo, Japan

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Publications (88)231.96 Total impact

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    ABSTRACT: Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The PD-1/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1-positive DLBCL. We performed PD-L1/PAX5 double immunostaining in 1,253 DLBCL biopsy samples and established a new definition of PD-L1-positive DLBCL. We also defined the criteria for microenvironmental PD-L1 (mPD-L1)-positive DLBCL, i.e., PD-L1-negative DLBCL in which PD-L1-positive nonmalignant cells are abundant in the tumor microenvironment. Of the 273 patients whose clinical information was available, quantitative analysis of PD-1-positive tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1-positive and mPD-L1-positive DLBCL were 11% and 15.3%, respectively. Both PD-L1- and mPD-L1-positive DLBCL were significantly associated with non-Germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1-positive TILs was significantly higher in GCB-type tumors and lower in mPD-L1- and PD-L1-positive DLBCL. Patients with PD-L1-positive DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1-negative DLBCL (P = 0.0009). In contrast, there was no significant difference in OS between mPD-L1-positive and -negative DLBCL (P = 0.31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = 0.0323). This is the first report describing the clinicopathological features and outcomes of PD-L1-positive DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup. Copyright © 2015 American Society of Hematology.
    No preview · Article · Aug 2015 · Blood
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    ABSTRACT: CD 20 positive myeloma with small lymphoplasmacytoid morphology is difficult to differentiate from mature B-cell lymphoma. A 71-year-old male was referred to our hospital because of osteolytic vertebral fractures and anemia. Urine was positive for Bence Jones protein, κ type. Bone marrow consisted of approximately 30% small lymphoplasmacytoid cells with scant cytoplasm, and these cells were positive for CD20, CD23 and CD138. FISH analysis revealed t(11;14)(CCND1/IGH). Myeloma with t(11;14) is closely associated with small lymphoplasmacytoid appearance and CD20 and CD23 expressions. The patient was diagnosed as having myeloma based on clinical and cytogenetic findings, and achieved VGPR (very good partial response) after treatment with lenalidomide.
    No preview · Article · Apr 2015 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: This retrospective study analyzes the results of radioimmunotherapy (RIT) with (90)Y-ibritumomab tiuxetan in 94 Japanese patients with relapsed or refractory low-grade B cell non-Hodgkin lymphoma at a single institution. All patients had previously been administered with 1-8 (median 1) regimens of rituximab alone or combined with other chemotherapeutic regimens at a mean age of 64 years. The overall response rate was 90 % and the complete response (CR) rate was 69 %. The median overall survival was not reached and progression-free survival (PFS) was 26 months, respectively, for the early phase 50 patients during a median follow-up period of 46.5 months. In this cohort, the PFS rates for the 50 early phase patients who had undergone ≤2 and ≥3 previous regimens, and for those who achieved CR compared with those who did not (partial response, PR; stable disease, SD; progressive disease, PD) were 38 and 11 months, respectively. Multivariate analysis showed that these two factors were statistically significant (p = 0.0011 and p <0.0001, respectively). The overall incidence of grade ≥3 non-hematological toxicity was 9 %. Two patients died of treatment-related deteriorating hepatitis C. A second malignancy developed in two patients at 10.5 and 3.5 months after treatment. We recommend administering (90)Y-ibritumomab tiuxetan as early in the disease course as possible, and at the latest as a third-line therapy to maximize the benefits of RIT, which should improve the quality of life for patients.
    No preview · Article · Aug 2014 · International Journal of Hematology
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    ABSTRACT: Primary effusion lymphoma (PEL) is a rare B-cell lymphoma, characterized by human herpes virus 8 (HHV8) infection and serous effusions without detectable tumor masses. However, cases with HHV8 unrelated PEL have also been reported, mainly in Japan, and these are referred to as PEL-like lymphoma (PEL-LL). We describe a 70-year-old man with cardiac comorbidity who developed PEL-LL with pleural effusion. The patient achieved a complete response (CR) after treatment with oral low-dose sobuzoxane and etoposide combined with rituximab. To date, the patient has been in CR for about 7 months without chemotherapy. PEL-LL reportedly has a better prognosis than PEL. Because PEL-LL is positive for CD20, unlike PEL, combination therapy including rituximab may be effective. PEL-LL mainly affects elderly people, so that further investigation of tolerable and effective regimens is required.
    No preview · Article · Jul 2014 · [Rinshō ketsueki] The Japanese journal of clinical hematology

  • No preview · Article · Sep 2013 · Leukemia & lymphoma
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    ABSTRACT: Erythropoiesis, a process of erythroid production, is controlled by several factors including oxygen level. In this study, the effect of oxygen tension on erythropoiesis was investigated in K562 erythroleukemic cell line and erythroid progenitor cells derived from normal and β-thalassemia/hemoglobin (Hb) E individuals. The enhanced erythroid differentiation specific markers including increased levels of α-, β- and γ-globin gene expressions, numbers of HbF positive cells and the presence of glycophorin A surface marker were observed during cell culture under hypoxic atmosphere. The result also showed that miR-210, one of the hypoxia-induced miRNAs, was up-regulated in K562 and β-thalassemia/HbE progenitor cells cultured under hypoxic condition. Inhibition of miR-210 expression leads to reduction of the globin gene expression and delayed maturation in K562 and erythroid progenitor cells. This indicated that miR-210 contributes to hypoxia-induced erythroid differentiation in both K562 cells and β-thalassemia/HbE erythroid progenitor cells.
    No preview · Article · Apr 2013 · Blood Cells Molecules and Diseases
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    ABSTRACT: Transfusion-related acute lung injury (TRALI) is a severe pulmonary complication following blood transfusions. We experienced a case of possible TRALI during the course of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). A 19-year-old woman was admitted to our hospital suffering from fever and abdominal pain. Her laboratory data revealed pancytopenia, liver damage, coagulopathy, and a high titer of EBV-DNA. Computed tomography showed hepatosplenomegaly and bone marrow aspiration revealed hemophagocytosis and the proliferation of atypical lymphocytes. A diagnosis of EBV-HLH was made and plasma exchange was performed. Severe hypoxia due to pulmonary edema developed two hours after starting the plasma transfusion. Methylprednisolone pulse therapy and non-invasive positive pressure ventilation ameliorated her respiratory condition. Anti-HLA class I and II antibodies were detected in donor sera and a cross-match test between patient lymphocytes and donor plasma was positive. To the best of our knowledge, this is the first case report of TRALI complicated with EBV-HLH. It is possible that hypercytokinemia accompanied by HLH was associated with the onset of TRALI.
    No preview · Article · Apr 2013 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: Background Allogeneic hematopoietic stem cell transplantation (HSCT) for patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is much more intensive than multi-agent combined chemotherapy, although allogeneic HSCT is associated with increased morbidity and mortality when compared with such chemotherapy. Minimal residual disease (MRD) status has been proven to be a strong prognostic factor for adult patients with Ph-negative ALL. Methods We investigated whether MRD status in adult patients with ALL is useful to decide clinical indications for allogeneic HSCT. We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL. Results Of 110 adult ALL patients enrolled between July 2002 and August 2008, 101 were eligible, including 59 Ph-negative patients. MRD status was assessed in 43 patients by the detection of major rearrangements in TCR and Ig and the presence of chimeric mRNA. Thirty-nine patients achieved CR1, and their probabilities of 3-year overall survival and disease-free survival (DFS) were 74% and 56%, respectively. Patients who were MRD-negative after induction therapy (n = 26) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 13; 69% vs. 31%, p = 0.004). All of 3 patients who were MRD-positive following consolidation chemotherapy and did not undergo allogeneic HSCT, relapsed and died within 3 years after CR. Conclusions These results indicate that MRD monitoring is useful for determining the clinical indications for allogeneic HSCT in the treatment of ALL in CR1.
    Full-text · Article · Feb 2013 · Journal of Hematology & Oncology
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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is characterized by deregulated engulfment of hematopoietic cells by bone marrow macrophages activated presumably by systemic inflammatory hypercytokinemia. We here show that the pathogenesis of HLH involves impairment of the anti-phagocytic system operated by interaction of surface CD47 and signal regulatory protein alpha (SIRPA). In HLH patients, the changes of expression levels, or HLH-specific polymorphism of SIRPA were not found. In contrast, the expression of surface CD47 was down-regulated specifically in HSCs in association with exacerbation of HLH, but not in healthy individuals. The number of bone marrow HSCs in HLH patients was reduced to ~20% of normal controls, and macrophages from normal donors aggressively engulfed HSCs purified from HLH patients but not those from normal controls in vitro. Furthermore, in response to inflammatory cytokines, normal HSCs, but not progenitors or mature blood cells, down-regulated CD47 sufficient to be engulfed by macrophages. The expression of pro-phagocytic calreticulin was kept suppressed at the HSC stage in both HLH and normal controls, even in the presence of inflammatory cytokines. These data suggest that the CD47-SIRPA anti-phagocytic system plays a key role in maintenance of HSCs, and that its disruption by HSC-specific CD47 down-regulation might be critical for HLH development.
    Preview · Article · Sep 2012 · Blood
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    ABSTRACT: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) leads to an aggressive and often fatal course without appropriate treatment. Etoposide therapy is crucial for the better prognosis, although it remains unknown what patients need cytotoxic agents. Since we have complied with step-up strategy in a tertiary center, treatment outcomes were studied to search predictors for disease course. The study enrolled 22 EBV-HLH patients treated between 1999 and 2010 in Kyushu University. Immunotherapy, chemotherapy and stem cell transplantation (SCT) proceeded in stages unless patients attained a consecutive >21 days-afebrile remission. Clinical and laboratory data and outcomes were retrospectively analyzed. Median age of 9 males and 13 females was 5 years (range: 9 months-41 years). Sixteen patients (73%) presented at age <15 years. Two patients remitted spontaneously, 12 attained remissions after immunotherapy, 5 after chemotherapy, and 1 after successful SCT. The remaining two patients died after chemotherapy and SCT, respectively. Median EBV load was 1 × 10(5) copies/ml of peripheral blood (range: 200-5 × 10(7)). T-cells were exclusively targeted (94%; 15/16 examined) often with EBV/T-cell receptor clonality. EBV status indicated 19 primary infections and 3 reactivations. Either death occurred in EBV-reactivated patients who underwent chemotherapy ± SCT. Age at primary infection in pediatric patients increased in the last 5 years. Patients having prolonged fever (P = 0.017) or high soluble CD25 levels (P = 0.017) at diagnosis were at higher risk for requiring chemotherapy assessed by multivariate analyses. No cytotoxic agents were needed for >60% of EBV-HLH patients. Early immunotherapy may modulate T-cell activation and reduce the chance of unnecessary chemotherapy.
    No preview · Article · Aug 2012 · Pediatric Blood & Cancer
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    ABSTRACT: We measured plasma levels of thrombopoietin (TPO) in several patients with thrombocytopenia. Similar to previous reports, TPO levels in aplastic anemia (N=9) were markedly higher than those in idiopathic thrombocytopenic purpura (N=10): 16.19+/-9.07 fmol/ml and 1.21+/-1.06 fmol/ml, respectively. In patients with secondary failure of platelet recovery (N=7) as well as primary failure after hematopoietic stem cell transplantation, TPO levels were very high, reflecting impaired platelet production due to GVHD, drug treatments, and infection. When using new drugs such as TPO-receptor agonists, measurement of TPO levels might be important to differentiate the mechanism of thrombocytopenia.
    No preview · Article · Jun 2012 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: Human immunodeficiency virus (HIV) infects CD4(+) lymphocytes, leading to a development of malignant lymphomas, such as HIV-associated Hodgkin Lymphoma (HIV-HL). This study aimed to assess the differences in cellular composition of the inflammatory reactive background of HIV-HLs. We examined infiltrating T lymphocytes, specifically regulatory T cells, cytotoxic cells, Epstein-Barr virus (EBV) related antigens and HIV-receptor CCR5. In all HIV-HL cases, Hodgkin and Reed-Sternberg (HRS) cells showed EBER1 expression, LMP-1 staining positivity and EBNA-2 staining negativity, except for one case which showed LMP-1 staining negativity. Our histological findings indicate the percentage of CD8(+) , TIA-1(+) lymphocytes was significantly higher in HIV-HL than in non-HIV-HL cases (P < 0.05). On the other hand, the percentage of CD4(+) , FOXP3(+) lymphocytes was significantly lower in HIV-HL than in non-HIV-HL cases (P < 0.05) but present. The percentage of CCR5(+) lymphocytes was significantly lower in HIV-HL than in non-HIV-HL cases (P < 0.05). Usually, CD4(+) and CCR5(+) lymphocytes are reported to be rarely detected in HIV-associated non-Hodgkin lymphomas, but the presence of CD4(+) and/or FOXP3(+) lymphocytes may be implicated in the pathogenesis of HL. In addition, although additional CD8(+) lymphocytes are probably not EBV-LMP specific cytotoxic T-cells, these lymphocytes may also well be involved in the pathogenesis of HIV-HL.
    No preview · Article · Feb 2012 · Pathology International
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    ABSTRACT: Virus-associated hemorrhagic cystitis (HC) is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although numerous studies have attempted to identify factors that predispose patients to viral HC, its causes remain controversial. We analyzed retrospectively the results of 266 allogeneic HSCTs to identify factors associated with HC. Of this group, 42 patients (15.8%) were diagnosed with viral HC, because of either adenovirus (ADV; n = 26; 9.8%) or BK virus (BKV; n = 16; 6.0%). ADV-HC was frequently associated with T cell purging, and was less common in patients with acute graft-versus-host-disease (GVHD). Conversely, BKV-HC was more frequently observed in patients with excessive immune reactions such as GVHD, preengraftment immune reaction, and hemophagocytic syndrome. These observations indicate that ADV- and BKV-HC may differ significantly in their risk factors and pathogenesis. Profound immune deficiency is more likely to be associated with ADV-HC, whereas immune hyperactivity might play a key role in BKV-HC.
    No preview · Article · Jul 2011 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: We report here a very severe case of thymoma-related aplastic anemia that developed after thymectomy. The patient was a 50-year-old man diagnosed with myasthenia gravis. Chest CT showed thymoma measuring 7.5 cm in diameter, and extended thymectomy was performed. Irradiation to the anterior mediastinum was added postoperatively. Thirteen months after surgery, hemogram showed severe neutropenia: leukocyte count 0.32×10(9)/l with 11% neutrophils; Hb 10.7 g/dl; and platelet count 100×10(9)/l. Although cyclosporine (CSP, 5 mg/kg/day) was administered, dose reduction was necessary because of renal damage. Cytopenia deteriorated to a leukocyte count of 0.71×10(9)/l with 21% neutrophils; Hb 5.9 g/dl; and platelet count 24×10(9)/l. However, addition of antithymocyte globulin (ATG, 15 mg/kg) led to hematopoietic recovery of all three lineages within one month. He is clinically stable with no transfusion requirement after 22 months with CSP maintenance therapy. Although thymoma-related aplastic anemia has been reported to have an extremely poor prognosis, high efficacy of CSP has been reported recently. In our case, ATG in combination with CSP was efficient. Adequate immunosuppressive therapy seems to be important for the clinical management of these patients.
    No preview · Article · May 2011 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV(+)LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV(+)LPD of childhood is not well described. Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34(+)stem cells following high purity cell sorting. Six Japanese patients with EBV(+)LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34(+)stem cells were studied by high-accuracy cell sorting (>99.5%), Southern blotting and real-time polymerase chain reaction. Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4(+)T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV(+)NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34(+)stem cells of patients. A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV(+)LPD of childhood. CD34(+)stem cells are spared, suggesting infection of more differentiated elements.
    No preview · Article · Mar 2011 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology

  • No preview · Article · Mar 2011 · The Lancet
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    ABSTRACT: Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. HTLV-1 is spread by cell-to-cell transmission via the gp46-197 region, from Asp197 to Leu216, in the envelope protein gp46. A correlation exists between the prevalence and titer of the antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the severity of ATLL. In the present study, immunohistochemical staining was performed on samples of paraffin embedded lymph nodes of three different histological types of ATLL (anaplastic large cell type, n = 10; pleomorphic type, n = 10; and Hodgkin's-like type, n = 10) from 30 cases and 10 cases of HTLV-associated lymphadenitis. Of the three ATLL subtypes, gp46 expression was highest in the anaplastic large cell type, followed by the pleomorphic type and Hodgkin's-like type (mean: 53.4%, 34.9% and 16.0%, respectively; P= 0.0003). In HTLV-1 associated lymphadenitis cases, gp46 positive cells were rarely seen (4.0%). These results suggest that gp46-197 immunohistochemical staining can be a useful histological indicator for prediction of the aggressiveness of ATLL and prognosis for ATLL patients.
    No preview · Article · Dec 2010 · Pathology International
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    ABSTRACT: Human herpes virus (HHV)6-associated limbic encephalitis and/or myelitis is one of the life-threatening central nervous system complications following allogeneic hematopoietic stem cell transplantation (HSCT). Recent reports have shown significant correlations of these complications with unrelated cord blood transplantation (UCBT). We retrospectively analyzed 228 allogeneic HSCT recipients in our single institution; 13 patients (5.7%) were diagnosed with HHV6-associated encephalitis/myelitis. This complication was documented in 8 of 51 UCBT recipients (15.7%) and 5 of 177 recipients (2.8%) transplanted with bone marrow or peripheral blood stem cells, indicating a higher incidence of this complication occurring in UCBT recipients (P = .0005). In addition, HHV6-associated encephalitis/myelitis occurred more frequently in recipients who underwent 2 or more HSCTs (7 of 59 recipients [11.9%]), compared to those who received only 1 HSCT (6 of 169 recipients [3.6%], P = .018). Of note, the incidence of this complication increased to 28.6% (6 of 21 recipients), when the analysis was restricted to a second or more UCBT recipients. All 13 patients presented preengraftment immune response prior to the onset of encephalitis. Two patients manifested typical symptoms at the onset of HHV6-associated encephalitis/myelitis, such as memory dysfunction, disorientation, and consciousness disturbance. However, 4 patients presented only with dysesthesia and pruritus, described as typical manifestations of patients with calcineurin-inhibitor-induced pain syndrome (CIPS), and the remaining 7 showed both symptoms, indicating that CIPS-like symptoms might be manifestations of HHV6-associated myelitis. Thus, physicians should be alert to this rare but often fatal complication, particularly for those who receive 2 or more HSCTs using UCB.
    Full-text · Article · Nov 2010 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: Vitamin K2 (VK2) can improve cytopenia in some patients with myelodysplastic syndrome (MDS). Although it is well known that VK2 induces differentiation and apoptosis in acute myeloid leukemia (AML) cell lines, little is known about its effect on normal hematopoietic progenitors. The effects of VK2 on primary myeloid and erythroid progenitors were examined. Mobilized CD34-positive cells from peripheral blood were used for the examination of myeloid lineage cells, and erythroid progenitors purified from peripheral blood were used for erythroid lineage cells. VK2 upregulated the expressions of myeloid markers CD11b and CD14, and increased the mRNA expression levels of CCAAT/enhancer binding protein-α (C/EBPα) and PU.1 in myeloid progenitors. In erythroid progenitors, VK2 did not show a significant effect on differentiation. However, VK2 exhibited an anti-apoptotic effect on erythroid progenitors under erythropoietin depletion. This anti-apoptotic effect was restricted to normal erythroid progenitors and was not shown in erythroleukemic cell line AS-E2. Steroid and xenobiotic receptor (SXR), which was recently identified as a receptor of VK2, was expressed on myeloid progenitors, and the SXR agonist rifampicin (RIF) also upregulated CD11b and CD14 expressions on myeloid progenitors. These results indicate that SXR is involved in the effect of VK2 on myeloid progenitors. The major effect of VK2 on myeloid progenitors was promoting differentiation, whereas its anti-apoptotic effect seemed to be dominant in erythroid progenitors. Although the detailed mechanism of VK2's effect on differentiation or apoptosis of hematopoietic progenitors remains unknown, the effect of VK2 therapy in patients with MDS could be partly explained by these mechanisms.
    No preview · Article · Sep 2010 · European Journal Of Haematology
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    ABSTRACT: Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].
    Full-text · Article · Jun 2010 · American Journal of Hematology

Publication Stats

849 Citations
231.96 Total Impact Points


  • 2015
    • National Cancer Center, Japan
      Edo, Tokyo, Japan
  • 2014
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 2013
    • Fukuoka National Hospital
      Hukuoka, Fukuoka, Japan
  • 1990-2013
    • Kyushu University
      • • Graduate School of Medical Sciences
      • • Division of Internal Medicine
      Hukuoka, Fukuoka, Japan
  • 2010
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan
  • 1998
    • Shin Kokura Hospital
      Kitakyūshū, Fukuoka, Japan