Colony‐stimulating factor‐1 (CSF‐1), also known as macrophage colony‐stimulating factor, controls the survival, proliferation, and differentiation of mono‐nuclear phagocytes and regulates cells of the female reproductive tract. It appears to play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, and myeloid and lymphoid tissues. Through alternative mRNA splicing and differential post‐translational proteolytic processing, CSF‐1 can either be secreted into the circulation as a glycoprotein or chondroitin sulfate‐containing proteoglycan or be expressed as a membrane‐spanning glycoprotein on the surface of CSF‐1‐producing cells. Studies with the op/op mouse, which possesses an inactivating mutation in the CSF‐1 gene, have established the central role of CSF‐1 in directly regulating osteoclastogenesis and macrophage production. CSF‐1 appears to preferentially regulate the development of macrophages found in tissues undergoing active morphogenesis and/or tissue remodeling. These CSF‐1 dependent macrophages may, via putative trophic and/or scavenger functions, regulate characteristics such as dermal thickness, male fertility, and neural processing. Apart from its expression on mononuclear phagocytes and their precursors, CSF‐1 receptor (CSF‐1R) expression on certain nonmononuclear phagocytic cells in the female reproductive tract and studies in the op/op mouse indicate that CSF‐1 plays important roles in female reproduction. Restoration of circulating CSF‐1 to op/op mice has preliminarily defined target cell populations that are regulated either humorally or locally by the synthesis of cell‐surface CSF‐1 or by sequestration of the CSF‐1 proteoglycan. The CSF‐1R is a tyrosine kinase encoded by the c‐fms proto‐oncogene product. Studies by several groups have used cells expressing either the murine or human CSF‐1R in fibroblasts to pinpoint the requirement of kinase activity and the importance of various receptor tyrosine phosphorylation sites for signaling pathways stimulated by CSF‐1. To investigate post‐CSF‐1R signaling in the macrophage, proteins that are rapidly phosphorylated on tyrosine in response to CSF‐1 have been identified, together with proteins associated with them. Studies on several of these proteins, including protein tyrosine phosphatase 1C, the c‐cbl proto‐oncogene product, and protein tyrosine phosphatase‐phi are discussed. Mol Reprod Dev 46:4–10, 1997. © 1997 Wiley‐Liss, Inc.

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Brain metastasis is a common and formidable challenge in patients with malignant melanoma. Although there have been no randomized controlled trials exclusively in patients with melanoma brain metastasis, care can be guided by the application of level I evidence for the treatment of brain metastasis in general and phase II studies focusing specifically on melanoma brain metastasis. Promising new agents and approaches are needed and will hopefully be identified in the near future.

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