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  • Burgering, B M T Bos, +27 authors R J Gbg
  • 1997
in vitro and in vivo association assays. The GST–cytoplasmic region of EGFR fusion proteins (amino acids 930–1,220, which do not include Lys 721, a key residue in the ATP-binding site) were generated as described 28. The in vitro Jak2 assay was done as before 2 , with minimal modification. Proteins immobilized on anti-Jak2 antibody were mixed with 95 ␮l of(More)
PURPOSE Inhibition of kinesin spindle protein or Eg5 causes the formation of monoastral mitotic spindles, which leads to cell death. AZD4877 is a specific, potent inhibitor of Eg5. METHODS This was a Phase I, open-label, two-part study to evaluate the maximum tolerated dose (MTD) and safety and tolerability of AZD4877 in patients with advanced solid(More)
OBJECTIVES To develop a method for drug dosing and pharmacokinetic (PK) sampling in children with cancer from a single indwelling central venous catheter that minimized drug contamination. METHODS A benchtop system was designed to simulate dosing and clearing actinomycin-D (AMD) and vincristine (VCR) from central venous catheters. The authors evaluated(More)
BACKGROUND Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. METHODS Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical(More)
CONTEXT Current treatment for acute myeloid leukemia (AML) in children cures about half the patients. Of the other half, most succumb to leukemia, but 5% to 15% die of treatment-related complications. Overweight children with AML seem to experience excess life-threatening and fatal toxicity. Nothing is known about how weight affects outcomes in pediatric(More)
PURPOSE To shorten the study conduct timeline of pediatric phase I oncology trials by employing a novel trial design. METHODS A comparison of the traditional 3 + 3 patients per cohort, phase I trial design with a novel, rolling six design was performed by using discrete event simulation. The rolling six design allows for accrual of two to six patients(More)
Actinomycin-D (Act-D) and vincristine (VCR) are cytotoxic agents commonly used in the treatment of pediatric cancers. To date, there are few published methods on quantifying Act-D or VCR and no published methods on quantifying the two drugs together. We present a methodology for the simultaneous quantification of Act-D and VCR in human plasma using liquid(More)
Actinomycin-D is an antineoplastic agent that inhibits RNA synthesis by binding to guanine residues and inhibiting DNA-dependent RNA polymerase. Although actinomycin-D has been used to treat rhabdomyosarcoma and Wilms tumor for more than 40 years, the dose/exposure relationship is not well characterized. The objective of this study was to develop an initial(More)
PURPOSE To determine the efficacy and safety of pediatric phase I oncology trials in the era of dose-intensive chemotherapy and to analyze how efficiently these trials are conducted. METHODS Phase I pediatric oncology trials published from 1990 to 2004 and their corresponding adult phase I trials were reviewed. Dose escalation schemes using fixed 30% dose(More)
The protein expression of the cyclin-dependent kinase inhibitor p27 is often deregulated in human tumors. In lymphomas the inactivation of p27 is achieved through either increased degradation(1) or sequestration via D cyclins,(2) and p27 protein levels have been shown to have a prognostic significance.(1,3) Recently, S-phase kinase-associated protein 2(More)