Experimental hematology
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Experimental hematology · Oct 2006
JTE-607, a multiple cytokine production inhibitor, ameliorates disease in a SCID mouse xenograft acute myeloid leukemia model.
Accumulating findings suggest that in acute myeloid leukemia (AML) patients, proinflammatory cytokines and growth factors play important roles in the proliferation and survival of AML cells in an autocrine and paracrine manner, leading to deterioration of AML. JTE-607 is a multiple cytokine inhibitor that potently suppresses production of proinflammatory cytokines. In the present study, we investigated the potency of JTE-607 as an antileukemic agent by exploiting a SCID mouse acute leukemia model. ⋯ Our results indicate that JTE-607 has potential to be a new class of antileukemic drug that exerts inhibitory activities against both the proliferation and proinflammatory cytokine production of AML cells.
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Experimental hematology · Oct 2006
Comparative Study Clinical TrialEvidence for downregulation of erythropoietin receptor in bone marrow erythroid cells of patients with chronic idiopathic neutropenia.
The aim of this study is to probe the mechanisms underlying anemia in patients with chronic idiopathic neutropenia (CIN) by evaluating parameters of bone marrow (BM) erythropoiesis. ⋯ Impaired BM erythropoiesis in CIN patients is probably the result of increased local production of TNF-alpha and IFN-gamma that induce apoptosis, cell growth inhibition, and downregulation of EPOR expression on erythroid cells. We suggest that anemia in CIN patients displays overlapping pathophysiologic features with anemia of chronic disease.
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Experimental hematology · Oct 2006
Clinical TrialIn vitro analysis of multipotent mesenchymal stromal cells as potential cellular therapeutics in neurometabolic diseases in pediatric patients.
Multipotent mesenchymal stromal cells (MSCs) play an important role in stromal support for hematopoietic stem cells, immune modulation, and tissue regeneration. We investigated their potential as cellular therapeutic tools in neurometabolic diseases as a growing number of affected children undergo to bone marrow transplantation. MSCs were isolated from bone marrow aspirates and expanded ex vivo under various culture conditions. ⋯ Taken together, we show that MSCs produce appreciable amounts of lysosomal enzyme activities, making these cells first-choice candidates for providing metabolic correction when given to enzyme-deficient patients. With the example of ASA, it was also shown that an enzyme secreted from MSCs is taken up by enzyme-deficient patient fibroblasts. Given the plasticity of MSCs, these cells represent an interesting add-on option for cellular therapy in children undergoing bone marrow transplantation for lysosomal storage diseases and other neurometabolic diseases.