Hemopoietic Growth Factors: A Review George Morstyn and Antony W. Burgess1

Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research,

Australia 3050 CANCER RESEARCH 48. 5624-5637, October 15. 1988

อาจารยท่ี์ปรกึษา : อาจารย ์ประสทิธิ ์ชนะรตัน์

Section 132 group 3

Hemopoietic system

Type of Colony stimulating factor

(CSF) Granulocyte-Macrophage Colony

Stimulating Factor (GM-CSF) Granulocyte Colony stimulating factor

(G-CSF) Macrophage Colony stimulating factor

(M-CSF) Multi Colony stimulating factor (multi-

CSF)

Colony stimulating factor Synthesis

Bone marrow + Cell line

Recombinant Natural cDNA of CSF Cell stimulation CFS Bacteria Stem cell

CSF Colonies Colony Testing

Granulocyte-Macrophage

Colony Stimulating Factor (GM-CSF)

Stimulated Granulocyte and Macrophage series in murine and human

Granulocyte Colony stimulating factor

(G-CSF) Human G -CSFSynthesized from recombinant DNA methodCan not diferented between natural G-CSF and recombinant G-CSF

Homology between human and murine G-CSF approximately 75 %

Differentiation of biological and species

Macrophage Colony stimulating factor

(M-CSF) Also called CSF-1 Active only in dimer form Human urinary M-CSF

stimulate for the final stages of granulocytic development in humans

stimulator of the early monocytic progenitor cells in mouse marrow

Murine M-CSFStimulate mouse marrow cell Not stimulate human marrow cell

Multi-Colony Stimulating Factor

(multi-CSF) Also called IL-3 Stimulate granulocyte ,macrophage and erythroid cell

Effects of Colony Stimulating Factors

on Mature Cells

In Vivo Effects of CSFs

Granulocyte-Macrophage Colony Stimulating FactorMurine studies increase in the peritoneum of neutrophils,monocytes, and eosinophils decrease in lymphocytes.Simian studies not restricted to the myeloid system

Multi-Colony Stimulating Factor

effects of multi-CSF in mice

peritoneal cavity increased of monocytes and these monocytes appeared to functionas more effective phagocytes.

Granulocyte Colony Stimulating Factor.

Hemopoietic Growth Factors and Leukemia CSFs suppression of normal

hemopoiesis by the leukemic cell of patients with acute myeloid leukemia ( AML)

Production and Storage of GM-CSF Most organs can produce the granulocyte

macrophage colony stimulating factors bioassays salivary gland, lung, thymus, kidney, spleen, lymph

node, pancreas, brain,heart, small intestine, testis, skeletal muscle, liver, and skin.

Endotoxin and tumor necrosis factor appear to stimulate CSF release

GM-CSF production by endothelial cells, smooth muscle, and fibroblasts and that these can be stimulated to produce CSF by tumor necrosis factor

GM-CSF is to identify the cells and tissues where GM-CSF mRNA is present

Clinical Disorders and Abnormal GM-

CSF Levels CSFs can control hemopoiesis in vivo direct and indirect

Correlation between urine CSF levels and WBC levels

Detected human G-CSF but not human GM-CSF

Early Clinical Trials with G-CSF

Future Directions

Clinical situations ; ovarian cancer ,lung cancerhigh concentrations GM-CSF inhibits the proliferation of small cell lung cancer cells.

Potential Side Effects of CSF

Therapy The direct effects of the colony stimulating factors will be confined to cells that contain CSF receptors

the stimulated cells may be induced to secrete other biological response modifiers which could in fluence the action of these molecules.

Another: potential side effect is the development of antibodies to CSF.

Thank you for your

questions