Hemopoietic growth factors


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Hemopoietic growth factors

  1. 1. Hemopoietic Growth Factors: A Review George Morstyn and Antony W. Burgess 1 Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Australia 3050 CANCER RESEARCH 48. 5624-5637, October 15. 1988 อาจารย์ที่ปรึกษา : อาจารย์ ประสิทธิ์ ชนะรัตน์ Section 132 group 3
  2. 2. Hemopoietic system
  3. 3. Type of Colony stimulating factor (CSF) <ul><li>Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) </li></ul><ul><li>Granulocyte Colony stimulating factor (G-CSF) </li></ul><ul><li>Macrophage Colony stimulating factor (M-CSF) </li></ul><ul><li>Multi Colony stimulating factor (multi-CSF) </li></ul>
  4. 4. Colony stimulating factor Synthesis <ul><li>Bone marrow + Cell line </li></ul><ul><li>Recombinant Natural </li></ul><ul><li>cDNA of CSF Cell stimulation </li></ul><ul><li>CFS </li></ul><ul><li>Bacteria Stem cell </li></ul><ul><li>CSF Colonies </li></ul><ul><li>Colony Testing </li></ul>
  5. 5. Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) <ul><li>Stimulated Granulocyte and Macrophage series in murine and human </li></ul>
  6. 6. Granulocyte Colony stimulating factor (G-CSF) <ul><li>Human G -CSF </li></ul><ul><ul><li>Synthesized from recombinant DNA method </li></ul></ul><ul><ul><li>Can not diferented between natural G-CSF and recombinant G-CSF </li></ul></ul><ul><ul><li>Homology between human and murine G-CSF approximately 75 % </li></ul></ul><ul><ul><li>Differentiation of biological and species </li></ul></ul>
  7. 7. Macrophage Colony stimulating factor (M-CSF) <ul><li>Also called CSF-1 </li></ul><ul><li>Active only in dimer form </li></ul><ul><li>Human urinary M-CSF </li></ul><ul><ul><li>stimulate for the final stages of granulocytic development in humans </li></ul></ul><ul><ul><li>stimulator of the early monocytic progenitor cells in mouse marrow </li></ul></ul><ul><li>Murine M-CSF </li></ul><ul><ul><li>Stimulate mouse marrow cell </li></ul></ul><ul><ul><li>Not stimulate human marrow cell </li></ul></ul>
  8. 8. Multi-Colony Stimulating Factor (multi-CSF) <ul><li>Also called IL-3 </li></ul><ul><li>Stimulate granulocyte ,macrophage and erythroid cell </li></ul>
  9. 9. Effects of Colony Stimulating Factors on Mature Cells
  10. 10. In Vivo Effects of CSFs <ul><li>Granulocyte-Macrophage Colony Stimulating Factor </li></ul><ul><li>Murine studies increase in the peritoneum of neutrophils,monocytes, and eosinophils decrease in lymphocytes. </li></ul><ul><li>Simian studies not restricted to the myeloid system </li></ul>
  11. 11. Multi-Colony Stimulating Factor effects of multi-CSF in mice peritoneal cavity increased of monocytes and these monocytes appeared to functionas more effective phagocytes.
  12. 12. Granulocyte Colony Stimulating Factor.
  13. 13. Hemopoietic Growth Factors and Leukemia <ul><li>CSFs suppression of normal hemopoiesis by the leukemic cell of patients with acute myeloid leukemia ( AML ) </li></ul>
  14. 14. Production and Storage of GM-CSF <ul><li>Most organs can produce the granulocyte macrophage colony stimulating factors bioassays </li></ul><ul><li>salivary gland, lung, thymus, kidney, spleen, lymph node, pancreas, brain,heart, small intestine, testis, skeletal muscle, liver, and skin. </li></ul><ul><li>Endotoxin and tumor necrosis factor appear to stimulate CSF release </li></ul><ul><li>GM-CSF production by endothelial cells, smooth muscle, and fibroblasts and that these can be stimulated to produce CSF by tumor necrosis factor </li></ul><ul><li>GM-CSF is to identify the cells and tissues where GM-CSF mRNA is present </li></ul>
  15. 15. Clinical Disorders and Abnormal GM-CSF Levels <ul><li>CSFs can control hemopoiesis in vivo direct and indirect </li></ul><ul><li>Correlation between urine CSF levels and WBC levels </li></ul><ul><li>Detected human G-CSF but not human GM-CSF </li></ul>
  16. 17. Early Clinical Trials with G-CSF
  17. 18. Future Directions <ul><li>Clinical situations ; ovarian cancer ,lung cancer </li></ul><ul><li>high concentrations GM-CSF inhibits the proliferation of small cell lung cancer cells. </li></ul>
  18. 19. Potential Side Effects of CSF Therapy <ul><li>The direct effects of the colony stimulating factors will be confined to cells that contain CSF receptors </li></ul><ul><li>the stimulated cells may be induced to secrete other biological response modifiers which could in fluence the action of these molecules. </li></ul><ul><li>Another: potential side effect is the development of antibodies to CSF. </li></ul>
  19. 20. Thank you for your questions