Learn More
PURPOSE Previous investigations have suggested that a subset of patients with metastatic cancer in a limited number of organs may benefit from local treatment. We investigated whether cancer patients with limited sites of metastatic disease (oligometastasis) who failed standard therapies could be identified and safely treated at one to five known sites of(More)
CDKN2/p16 inhibits the cyclin D/cyclin-dependent kinase complexes that phosphorylate pRb, thus blocking cell cycle progression. We previously reported that p16 levels are low to undetectable in normal human uroepithelial cells (HUCs) and in immortalized uroepithelial cells with functional pRb, whereas p16 levels are markedly elevated in immortal HUCs with(More)
The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and Drug(More)
PURPOSE Given their accessibility, surrogate tissues, such as peripheral blood mononuclear cells (PBMC), may provide potential predictive biomarkers in clinical pharmacogenomic studies. In leukemias and lymphomas, the prognostic value of peripheral blast expression profiles is clear; however, it is unclear whether circulating mononuclear cells of patients(More)
A precise contrast agent (CA) arterial input function (AIF) is important for accurate quantitative analysis of dynamic contrast-enhanced (DCE)-MRI. This paper proposes a method to estimate the AIF using the dynamic data from multiple reference tissues, assuming that their AIFs have the same shape, with a possible difference in bolus arrival time. By(More)
Expression profiling has demonstrated that transcriptomes of primary malignancies differ from those in normal tissue. It is unknown, however, whether there exist "surrogate" transcriptional markers in peripheral blood mononuclear cells (PBMCs) of patients with solid tumors. We identified transcripts expressed differentially between PBMCs from renal cell(More)
PURPOSE This was a phase I trial to determine the maximum tolerated dose and toxicity of deforolimus (AP23573, MK-8669), an inhibitor of mammalian target of rapamycin (mTOR). The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. EXPERIMENTAL DESIGN Deforolimus was administered intravenously over 30 min every 7 days(More)
OBJECTIVE Uncovering the dominant molecular deregulation among the multitude of pathways implicated in aggressive prostate cancer is essential to intelligently developing targeted therapies. Paradoxically, published prostate cancer gene expression signatures of poor prognosis share little overlap and thus do not reveal shared mechanisms. The authors(More)
In dynamic contrast-enhanced MRI (DCE-MRI) studies, an accurate knowledge of the arterial contrast agent concentration as a function of time is crucial for the estimation of kinetic parameters. In this work, a novel method for estimating the arterial input function (AIF) based on the contrast agent concentration-vs.-time curves in two different reference(More)
PURPOSE Hypertension is a mechanism-based toxicity of sorafenib and other cancer therapeutics that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. This prospective, single-center, cohort study characterized ambulatory blood pressure monitoring as an early pharmacodynamic biomarker of VEGF signaling pathway inhibition by sorafenib.(More)