This Phase I application is concerned with the secretion of (G-CSF by bone marrow mononuclear cells and its stimulation by a combination of retinoids and natural product extract from a Chinese fungus (""""""""fungal extract"""""""": FE). Retinoids are used clinically to prevent and treat certain types of cancers while the FE is used in traditional Chinese medicine to reduce the myelotoxicity of high dose chemotherapy and radiation therapy. These investigators have already shown that FE stimulates human CFU-GM and that it also stimulates the release of cytokines from bone marrow cells. They have also shown that all-trans retinoic acid potentiated the stimulation of G-CSF secretion by FE, while inhibiting the induced secretion of (GM-CSF and TNF-alpha in a dose- dependent fashion. Other retinoids were also active, including 9-cis retinoic acid as well as vitamin D3. The effect was not, however, a non- specific result of exposure to steroids, since T3 and beta-estradiol did not shown similar effects. The investigators now will elucidate the mechanism of interaction between retinoids and FE in inducing (3-CSF secretion.
