Clinical application of human urinary colony-stimulating factor.

点击翻译按钮获取中文摘要

Human urinary colony-stimulating factor(CSF-HU)is one of adherent cell dependent CSFs, which stimulates human peripheral blood monocytes to produce human granulocytic colony-stimulating factor (G-CSF) that stimulates human granulocytic colony-forming cells (G-CFCs) to from granulocytic colonies in a monolayer agar culture. In this research project, we have tried to purify CSF-HU and use it on patients with cancer as an antigranulocytopenic drug. We have extensively purified CSF-HU using the procedure containing DEAE cellulose column, gel filtration, phenyl-Sepharose column, and chromatofocusing and reversed phase HPLC (high performance liquid chromatography) and obtained almost pure CSF-HU of which specific activity was 1.9x10 U/mg protein. We now analyze N-terminal amino acid sequence of this material and establish radioimmunoassay system for CSF-HU using purified CSF-HU and polyclonal antibody against partially purified CSF-HU. CSF-HU did not stimulate cell growth of several human leukemic cell lines and fresh leukemic cells. Preparation I of CSF-HU which we previously used in clinical trials, had partially protected the patients from granulocytopenia after anticancer chemotherapies but it gave several side effects such as fever and chilliness. We have further purified and obtained preparation II of CSF-HU which was 6 fold-higher specific activity and 15 fold-lower endotoxin content. We injected 33 patients with 8x10 U of preparation II for 7 days after the end of chemotherapies. Average granulocyte nadir of 33 patients was 896 871 in preparation II-injected courses and 494 336 in control courses. Duration under 500 granulocytes was 2.9 3.8 days in preparation II-infused courses and 4.7 3.7 days in control courses. These differences were statistically significant. Based on these observations, double blind phase III clinical study will be initiated in near future.