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Clinical Course and Flow Cytometric Analysis of Paroxysmal Nocturnal Hemoglobinuria in the United States and Japan
Important differences between white and Asian patients with PNH are identified and identification of prognostic factors will help the design of prospective clinical trials for PNH. Expand
NKG2D Initiates Caspase-Mediated CD3ζ Degradation and Lymphocyte Receptor Impairments Associated with Human Cancer and Autoimmune Disease
Analysis of ex vivo phenotypes of T and NK cells among tumor-infiltrating lymphocytes and in peripheral blood from patients with juvenile-onset lupus indicates that pathological NKG2D ligand expression leads to simultaneous impairment of multiple CD3ζ-dependent receptor functions, thus offering an explanation that may be applicable to CD3 ε deficiencies associated with diverse disease conditions. Expand
The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML
It is suggested that PI-103 actively enhances downstream p53 signaling and that a combination strategy aimed at inhibiting PI3K/Akt/mTOR signaling and activating p53 signaled is potentially effective in AML, where TP53 mutations are rare and downstream p 53 signaling is intact. Expand
Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with…
The findings provide the molecular rationale for concomitant targeting of Aurora kinases and Mdm2 in AML where TP53 mutations are rare and downstream p53 signaling is mostly intact. Expand
Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome.
Granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS antibody in vitro, which supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders. Expand
PIG-W is critical for inositol acylation but not for flipping of glycosylphosphatidylinositol-anchor.
- Y. Murakami, Uamporn Siripanyapinyo, +5 authors T. Kinoshita
- Biology, Medicine
- Molecular biology of the cell
- 13 June 2003
Many cell surface proteins are anchored to a membrane via a glycosylphosphatidylinositol (GPI), which is attached to the C termini in the endoplasmic reticulum. The inositol ring of… Expand
Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP.
- N. Hanaoka, T. Kawaguchi, K. Horikawa, S. Nagakura, H. Mitsuya, H. Nakakuma
- Biology, Medicine
- 1 February 2006
It is shown that leukemic K562 cells preferentially survived natural killer (NK) cell-mediated cytotoxicity in vitro when they acquired PIGA mutations, which is ascribable to the deficiency of stress-inducible GPI-linked membrane proteins ULBP1 and ULBP2, which activate NK and T cells. Expand
Eμ/miR-125b transgenic mice develop lethal B-cell malignancies
The results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells in vitro and in vivo and identify Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene in hematopoietic cells in vivo. Expand
Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS Clinical Trial
- Y. Kanakura, K. Ohyashiki, +13 authors M. Omine
- International journal of hematology
- 12 January 2011
The AEGIS results demonstrate that eculizumab is effective, safe and well tolerated in Japanese patients with PNH and reduces intravascular hemolysis with high statistical significance. Expand