Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by new indolinone derivatives targeting fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor receptors.

In acute myeloid leukemia (AML), receptor tyrosine kinase ligands promote growth and survival and contribute to AML-associated marrow neoangiogenesis. We have tested simultaneous inhibition of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptor signaling by novel indolinone derivatives using 14 myeloid, including 11 human leukemic, cell lines. Compounds inhibited colony formation of all cell lines in a dose-dependent fashion.

Receptor for platelet-activating factor (PAF) is not detectable by flow cytometry on the surface of myeloid leukemic cells.

Flow cytometry was applied to test for platelet-activating-factor receptor (PAF-R) presence on the membranes of acute myeloid leukemia (AML) cells. We have used six human AML cell lines and freshly taken density gradient separated blasts from the bone marrow of ten AML patients covering the majority of French-American-British (FAB) subtypes. Additionally, we have used one histiocytic lymphoma cell line and mature human granulocytes/monocytes as controls.

Influence of keratinocyte growth factor on clonal growth of epithelial tumor cells, lymphoma and leukemia cells and on sensitivity of tumor cells towards 5-fluorouracil in vitro.

RhKGF is developed for prevention and treatment of chemotherapy- and radiation-induced epithelial damage in cancer patients. Little information exists on growth modulation of malignant cells by KGF. We have tested the anchorage-independent clonal growth of 35 human tumor and 22 lymphoma and leukemia cell lines in semisolid media with or without rhKGF.