Other
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Other InterestsNature Medicine, Cell Metabolism, JCI
Publications (59) View all
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Article: Clinical efficacy of high-dose cepharanthine for idiopathic thrombocytopenic purpura: retrospective multicenter analysis.
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ABSTRACT: Cepharanthine (CEP), an alkaloid drug that has a cell membrane stabilizing effect and an immunomodulating effect, has been reported to improve symptoms and signs of chronic immune thrombocytopenia (ITP). In this study, we retrospectively assessed the clinical efficacy and adverse events of high-dose CEP for 47 patients with ITP. The response rate (elevation of platelet count>5×10(4)/μl) was 44%, and CEP treatment was judged useful in clinical aspects by their attending doctors in 77% of the cases. Next, we made a comparative analysis between patients who were administered CEP as a single agent (22 patients) and those administered CEP in combination therapy with prednisolone (PSL) (20 patients). There was a marked increase in platelet count in both groups compared to the count before CEP treatment (P<0.01), and no significant difference was seen between the two groups. High-dose CEP was well tolerated, and in some patients single-agent CEP therapy resulted in a significant elevation of platelets, allowing a reduced dosage of PSL.[Rinshō ketsueki] The Japanese journal of clinical hematology 12/2012; 53(12):1983-90. -
Article: Outcome of medium-dose VP-16/CY/TBI superior to CY/TBI as a conditioning regimen for allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia.
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ABSTRACT: The choice of conditioning regimen before allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia (ALL) is important. We retrospectively compared outcomes of medium-dose VP-16/cyclophosphamide/total body irradiation (VP/CY/TBI) regimen and CY/TBI. Five hundred and twenty-nine patients (VP/CY/TBI: n = 35, CY/TBI: n = 494) who met all of the following criteria were compared: first time for SCT, aged 15-59 years; first or second complete remission at SCT; bone marrow or peripheral blood as stem cell source; and HLA phenotypically matched donor. Median age of the patients was 34 years, and patients who received VP/CY/TBI were younger (28 vs. 34 years, P = 0.02). Cumulative incidences of relapse and non-relapse mortality (NRM) were higher for patients who received CY/TBI (P = 0.01 for relapse, P < 0.01 for NRM). After a median follow-up period of 36.9 months, 5-year overall survival (OS) rates were 82.2% in the VP/CY/TBI group and 55.2% in the CY/TBI group. OS, and disease-free survival (DFS) in the VP/CY/TBI group were shown to be significantly better by multivariate analysis [hazard ratio: 0.21 (95% confidence interval: 0.06-0.49) for DFS, hazard ratio: 0.25 (95% confidence interval: 0.08-0.59) for OS]. VP/CY/TBI was associated with a lower relapse rate and no increase in NRM, resulting in better survival than that in CY/TBI for adult ALL patients.International journal of hematology 11/2011; 94(5):463-71. · 1.17 Impact Factor -
Article: Comparison of unrelated cord blood transplantation and HLA-mismatched unrelated bone marrow transplantation for adults with leukemia.
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ABSTRACT: Recent advances in unrelated cord blood transplantation (UCBT) and high-resolution typing of human leukocyte antigen (HLA) from an unrelated donor have increased choices in alternative donor/stem cell source selection. We assessed HLA-mismatched locus-specific comparison of the outcomes of 351 single-unit UCB and 1,028 unrelated bone marrow (UBM) adult recipients 16 years old or older at the time of transplantation who received first stem cell transplantation with myeloablative conditioning for acute leukemia or myelodysplastic syndromes. With adjusted analyses, HLA 0 to 2 mismatched UCBT showed similar overall mortality (relative risk [RR] = 0.85, 95% confidence interval [CI], 0.68-1.06; P = .149) compared with that of single-HLA-DRB1-mismatched UBMT. UCBT showed inferior neutrophil recovery (RR = 0.50, 95% CI, 0.42-0.60; P < .001), lower risk of acute graft-versus-host disease (RR = 0.55, 95% CI, 0.42-0.72; P < .001), and lower risk of transplantation-related mortality (RR = 0.68, 95% CI, 0.50-0.92; P = .011) compared with single-HLA-DRB1-mismatched UBMT. No significant difference was observed for risk of relapse (RR = 1.28, 95% CI, 0.93-1.76; P = .125). HLA 0 to 2 antigen-mismatched UCBT is a reasonable second alternative donor/stem cell source with a survival outcome similar to that of single-HLA-DRB1-mismatched or other 7 of 8 UBMT.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2011; 18(5):780-7. · 3.15 Impact Factor -
Article: Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance.
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ABSTRACT: Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg(-/-)), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg(-/-) mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.Proceedings of the National Academy of Sciences 03/2011; 108(14):5753-8. · 9.68 Impact Factor -
Article: Enhancement of drug absorption through the blood-brain barrier and inhibition of intercellular tight junction resealing by E-cadherin peptides.
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ABSTRACT: E-cadherin-mediated cell-cell interactions in the zonula adherens play an important role in the formation of the intercellular tight junctions found in the blood-brain barrier. However, it is also responsible for the low permeation of drugs into the brain. In this study, HAV6 peptide derived from the EC1 domain of E-cadherin was found to enhance the permeation of ¹⁴C-mannitol and [³H(G)]-daunomycin through the blood-brain barrier of the in situ rat brain perfusion model. In addition, HAV6 peptide and verapamil have a synergistic effect in enhancing the BBB permeation of daunomycin. A new intercellular-junction resealing assay was also developed using Caco-2 monolayers to evaluate new peptides (BLG2, BLG3, and BLG4) derived from the bulge regions of the EC2, EC3, and EC4 domains of E-cadherin. BLG2 and BLG4 peptides but not BLG3 peptides were found to be effective in blocking the resealing of the intercellular junctions. The positive control peptides (ADT10, ADT6, and HAV10) block the resealing of the intercellular junctions in a concentration-dependent manner. All these findings suggest that E-cadherin-derived peptides can block E-cadherin-mediated cell-cell interactions. These findings demonstrate that cadherin peptides may offer a useful targeted permeation enhancement of therapeutic agents such as anticancer drugs into the brain.Molecular Pharmaceutics 02/2011; 8(1):239-49. · 4.78 Impact Factor
