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Year:
1998
| Volume: 6
| Issue: 3
| Pages: 115-117
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Review Article |
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MODULATION OF STEM CELL PROLIFERATION BY ANTICYTOKINE OR ANTISENSE OLIGONUCLEOTIDE STRATEGY IN HEMATOLOGICAL MALIGNANCIES
Pavle MILENKOVIC |
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DOI:
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Abstract: |
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Continuous proliferation and differentiation of hemopoietic cells are controlled by complex interactions and genetically determined production of stimulatory and inhibitory regulatory molecules. In hematological malignancies clonal expansion of transformed hemopoietic stem cells (HSC) is related to changes in oncogene expression (ras, myc, fos, mpl, kit...) leading to impaired production/response to regulatory molecules. In recent years a number of diverse therapy strategies have been evaluated in the development of novel therapeutic modalities. Selected approaches involve cytokine/anticytokine, antisense oligonucleotide, inhibition of intracellular signal transduction and gene therapy. Reduction of the level or activity of cytikines as cell viability factors (inhibitors of cytikine synthesis, antibodies to cytokine receptors...) consequently enhances and induces apoptotic action of hemotherapeutic agent. The use of antisense oligonucleotides ( c-myb or c-myc antisense oligonucleotides, inhibition of bcl-2, reversal of multidrug resistance by mdr1 antisense oligonucleotide...) are currently extensively studied in vitro and in vivo. New approaches in inhibition of intracellular signal transduction involve a down regulation of oncogene expression. More specific studies involve potentials of gene-target selective destruction of leukemic cells containing bcr-c-abl fusion gene. |
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Key words:
CYTOKINES+antagonists and inhibitors; APOPTOSIS+drug effects; RECEPTORS, INTERLEUKIN-1+antagonists and inhibitors; OLIGONUCLEOTIDES, ANTISENSE; HEMATOLOGIC NEOPLASMS |
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