Jonasch E.,University of Texas M. D. Anderson Cancer Center |
McCutcheon I.E.,University of Texas M. D. Anderson Cancer Center |
Waguespack S.G.,University of Texas M. D. Anderson Cancer Center |
Wen S.,University of Texas M. D. Anderson Cancer Center |
And 6 more authors.
Annals of Oncology | Year: 2011
Background: Von Hippel-Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluated the safety and efficacy of sunitinib in VHL patients and examined the expression of candidate receptors in archived tissue. Methods: Patients with VHL were given four cycles of 50 mg sunitinib daily for 28 days, followed by 14 days off. Primary end point was toxicity. Modified RECIST were used for efficacy assessment. We evaluated 20 archival renal cell carcinomas (RCCs) and 20 hemangioblastomas (HBs) for biomarker expression levels using laser-scanning cytometry (LSC). Results: Fifteen patients were treated. Grade 3 toxicity included fatigue in five patients. Dose reductions were needed in 10 patients. Eighteen RCC and 21 HB lesions were evaluable. Six of the RCCs (33%) responded partially, versus none of the HBs (P = 0.014). LSC revealed that mean levels of phosphorylated vascular endothelial growth factor receptor-2 were lower in HB than in RCC endothelium (P = 0.003) and mean phosphorylated fibroblast growth factor receptor substrate-2 (pFRS2) levels were higher in HB (P = 0.003). Conclusions: Sunitinib treatment in VHL patients showed acceptable toxicity. Significant response was observed in RCC but not in HB. Greater expression of pFRS2 in HB tissue than in RCC raises the hypothesis that treatment with fibroblast growth factor pathway-blocking agents may benefit patients with HB. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Li X.,University of Maryland Baltimore County |
Rao V.,University of Maryland Baltimore County |
Jin J.,University of Maryland Baltimore County |
Guan B.,University of Maryland Baltimore County |
And 3 more authors.
Journal of Proteome Research | Year: 2012
Regulation of all cellular processes requires dynamic regulation of protein phosphorylation. We have developed an unbiased system to globally quantify the phosphorylation index for substrates of a specific kinase by independently quantifying phosphorylated and total substrate molecules in a reverse in-gel kinase assay. Non-phosphorylated substrate molecules are first quantified in the presence and absence of a specific stimulus. Total substrate molecules are then measured after complete chemical dephosphorylation, and a ratio of phosphorylated to total substrate is derived. To demonstrate the utility of this approach, we profiled and quantified changes in phosphorylation index for Protein Kinase CK2 substrates that respond to a small-molecule inhibitor. A broad range of inhibitor-induced changes in phosphorylation was observed in cultured cells. Differences among substrates in the kinetics of phosphorylation change were also revealed. Comparison of CK2 inhibitor-induced changes in phosphorylation in cultured cells and in mouse peripheral blood lymphocytes in vivo revealed distinct kinetic and depth-of-response profiles. This technology provides a new approach to facilitate functional analyses of kinase-specific phosphorylation events. This strategy can be used to dissect the role of phosphorylation in cellular events, to facilitate kinase inhibitor target validation studies, and to inform in vivo analyses of kinase inhibitor drug efficacy. © 2012 American Chemical Society.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 198.81K | Year: 2011
Rare cell sublets in peripheral blood, such as circulating tumor cells (CTCs) has been used as biomarkers for cancer progression. In addition, growing evidence suggests that CTC isolation from a blood sample may allow reliable early detection and molecularcharacterization of cancer at diagnosis or relapse and provide a minimally-invasive method to guide and monitor the results of cancer therapy in cancer patients. Our goal is to commercialize a cost effective point of care device capable of isolating viable CTCs from a wide variety of cancers, for which proof of concept has been achieved in a research setting. For this Phase I proposal, we aim (1) to demonstrate the device feasibility for antibody independent isolation of viable CTCs, (2) to compare performance against the current FDA approved, state-of-the-art CTC isolation technology,and (3) characterize system performance. With the introduction of this technology, CTCs can be isolated from all metastatis cancers and provide a pre-screen diagnostic tool for cancer patients in a point of care setting. Also, unpurterbed and viable state of CTCs will allow systematic biological analysis of individual cells, permitting a personalized approach to cancer therapy.
Apocell Inc. | Date: 2011-06-01
Apocell Inc. | Date: 2010-06-04
specimen collection kit.