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Abstract  Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm that usually affects infants and young children. In this report, we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid (CSF) of an infant with AT/RT. These cells retained the morphological and biomarker characteristics of the original tumor. A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4, Insulin-R, PDGFR and IGF-IR, which appear to depend on Hsp90 to maintain their active form. IGF-IR activity is consistent with data from other established AT/RT cell lines. Inhibition of IGF-IR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells. In addition, neutralizing antibodies to IGF-II also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine. We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells. In addition to previously described cell lines and xenograft models, continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumor. [ABSTRACT FROM AUTHOR]

Stromal cells from a child with constitutional trisomy 8 who developed myelodysplastic syndrome (MDS) were found to produce abnormal levels of various cytokines, including VEGF, and supported the growth of leukemic cells in co-culture assays. This study shows that the geldanamycin derivative 17-AAG effectively reduces the VEGF expressions by MDS stromal cells. In co-culture experiments this agent also block the ability of the MDS stromal cells to stimulate the growth of leukemic cells. These data provide important initial evidence for the effect of 17-AAG on the marrow microenvironment and its potential use in the treatment of MDS and leukemia. [ABSTRACT FROM AUTHOR]