Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraperitoneal injection of a replication-deficient adenovirus containing the HST-1 (FGF-4) gene (Adex1HST-1) increased peripheral platelet counts in mice, and also effectively prevented experimentally induced thrombocytopenia. Here, we report the therapeutic potential of Adex1HST-1 on severely injured mice after exposure to otherwise lethal irradiation. Eighteen out of 20 mice that received Adex1HST-1 prior to gamma-irradiation (9 Gy) survived, while all the 20 mice with prior administration of control adenoviruses died after irradiation (P<0.0001). Hematological and histopathological analyses revealed that Adex1HST-1 acts as a potent protector against lethal irradiation, which causes injury of intestinal tract as well as myelosuppression in the bone marrow and spleen. These data demonstrate that the protective effects of administration of Adex1HST-1 against irradiation are superior to any other protective effects of cytokines against a lethal dose of irradiation, and that the pre-administration of Adex1HST-1 may be useful for lessening the side effects of currently used chemo- and radio-therapy against cancer.
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PMID:Adenovirus-mediated transfer of HST-1/FGF-4 gene protects mice from lethal irradiation. 1055 81

The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.
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PMID:Local signals in stem cell-based bone marrow regeneration. 1647 33