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Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals(More)
PURPOSE The primary objectives of this trial were to define the maximum tolerated dose (MTD) and to characterize the toxicities and pharmacokinetics of depsipeptide (FR901228) given on a day-1 and day-5 schedule every 21 days. A secondary objective of the trial was to seek evidence of antineoplastic activity. PATIENTS AND METHODS Patients with advanced or(More)
BACKGROUND ABT-737 is a pan-Bcl-2 inhibitor that has a wide range of single-agent activity against acute lymphoblastic leukemia (ALL) cell lines and xenografts. A relationship between expression of myeloid cell leukemia 1 (Mcl-1), an antiapoptotic member of the Bcl-2 family of proteins, and resistance to ABT-737 has been reported for various cancers. The(More)
BACKGROUND MLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis. PROCEDURES MLN8237 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0 nM(More)
10009 Background: Fenretinide (4-HPR), a cytotoxic retinoid, achieved limited and variable plasma levels when tested in a corn oil-based capsule. 4HPR/Lym-X-Sorb (LXS) oral powder is a new formulation intended to increase bioavailability, especially in children. METHODS This trial sought to define the toxicities, dose limiting toxicities (DLTs), maximum(More)
AIMS The involvement of cytokines in the aqueous humour is important in the development and progression of diabetic macular oedema (DMO) and macular oedema (MO) due to branch retinal vein occlusion (BRVO-MO). In this study, the concentrations of cytokines in the aqueous humour of eyes with DMO and BRVO-MO were measured and compared. METHODS Prospective,(More)
Defects in apoptosis signaling contribute to poor outcome in pediatric acute lymphoblastic leukemia (ALL), and overexpression of antiapoptotic Bcl-2 (Bcl-2 and Bcl-X(L)) family proteins has been observed in ALL. ABT-737 is a small-molecule BH3-mimetic that inhibits the antiapoptotic Bcl-2 family proteins. We evaluated the cytotoxicity of ABT-737 in(More)
BACKGROUND PSC 833 is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance (MDR). The authors conducted a Phase I study of orally administered PSC 833 in combination with vinblastine administered as a 5-day continuous infusion. METHODS Seventy-nine patients with advanced malignant disease were enrolled in the trial(More)
BACKGROUND Sorafenib is an inhibitor of multiple kinases (e.g., VEGF receptors, PDGFR, FLT3, RET, BRAF, KIT) and is approved by FDA for treatment of two adult cancers. The activity of sorafenib was evaluated against the PPTP's in vitro and in vivo panels. PROCEDURES Sorafenib was evaluated against the PPTP in vitro panel using 96-hr exposure at(More)
BACKGROUND MK-8242 is an inhibitor of MDM2 that stabilizes the tumor suppressor TP53 and induces growth arrest or apoptosis downstream of TP53 induction. PROCEDURES MK-8242 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10.0 μM and against the PPTP in vivo xenograft panels(More)