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61 results on '"Sprowl, Jason A"'

53. CYP3A4*22 Genotype and Systemic Exposure Affect Paclitaxel-Induced Neurotoxicity

Author

de Graan, Anne-Joy M., primary, Elens, Laure, additional, Sprowl, Jason A., additional, Sparreboom, Alex, additional, Friberg, Lena E., additional, van der Holt, Bronno, additional, de Raaf, Pleun J., additional, de Bruijn, Peter, additional, Engels, Frederike K., additional, Eskens, Ferry A.L.M., additional, Wiemer, Erik A.C., additional, Verweij, Jaap, additional, Mathijssen, Ron H.J., additional, and van Schaik, Ron H.N., additional

Published
2013
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54. Proximal Tubular Secretion of Creatinine by Organic Cation Transporter OCT2 in Cancer Patients

Author

Ciarimboli, Giuliano, primary, Lancaster, Cynthia S., additional, Schlatter, Eberhard, additional, Franke, Ryan M., additional, Sprowl, Jason A., additional, Pavenstädt, Hermann, additional, Massmann, Vivian, additional, Guckel, Denise, additional, Mathijssen, Ron H. J., additional, Yang, Wenjian, additional, Pui, Ching-Hon, additional, Relling, Mary V., additional, Herrmann, Edwin, additional, and Sparreboom, Alex, additional

Published
2012
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55. Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells

Author

Sprowl, Jason A, primary, Reed, Kerry, additional, Armstrong, Stephen R, additional, Lanner, Carita, additional, Guo, Baoqing, additional, Kalatskaya, Irina, additional, Stein, Lincoln, additional, Hembruff, Stacey L, additional, Tam, Adam, additional, and Parissenti, Amadeo M, additional

Published
2012
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60. Uptake Carriers and Oncology Drug Safety

Author

Sprowl, Jason A. and Sparreboom, Alex

Abstract

Members of the solute carrier (SLC) family of transporters are responsible for the cellular influx of a broad range of endogenous compounds and xenobiotics in multiple tissues. Many of these transporters are highly expressed in the gastrointestinal tract, liver, and kidney and are considered to be of particular importance in governing drug absorption, elimination, and cellular sensitivity of specific organs to a wide variety of oncology drugs. Although the majority of studies on the interaction of oncology drugs with SLC have been restricted to the use of exploratory in vitro model systems, emerging evidence suggests that several SLCs, including OCT2 and OATP1B1, contribute to clinically important phenotypes associated with those agents. Recent literature has indicated that modulation of SLC activity may result in drug-drug interactions, and genetic polymorphisms in SLC genes have been described that can affect the handling of substrates. Alteration of SLC function by either of these mechanisms has been demonstrated to contribute to interindividual variability in the pharmacokinetics and toxicity associated with several oncology drugs. In this report, we provide an update on this rapidly emerging field.

Published
2014
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61. Changes in expression of cell wall turnover genes accompany inhibition of chromosome segregation by bovine protein kinase C alpha expression in Saccharomyces cerevisiae.

Author

Sprowl JA, Villeneuve DJ, Guo B, Young AJ, Hembruff SL, and Parissenti AM

Subjects
Animals, Cattle, Cell Division, Cell Proliferation, G2 Phase, Gene Expression Profiling, Immunoblotting, Mitosis, Oligonucleotide Array Sequence Analysis, Phosphoprotein Phosphatases metabolism, Polymerase Chain Reaction, RNA, Fungal, Saccharomyces cerevisiae Proteins genetics, Spindle Apparatus, Cell Wall metabolism, Chromosome Segregation, Gene Expression Regulation, Fungal physiology, Protein Kinase C-alpha genetics, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae Proteins metabolism
Abstract

Expression of bovine PKCalpha in Saccharomyces cerevisiae results in growth inhibition, which is strongly augmented upon addition of phorbol esters. To investigate the nature of this PKC-induced inhibition of cell growth, wildtype and bovine PKCalpha-expressing yeast cells were examined by flow cytometry and by fluorescence microscopy after staining with propidium iodide. Upon expression and activation of the mammalian PKC isoform, cells accumulated in the G2/M phase of the cell cycle and exhibited impaired chromsome segregation. In some instances, PKC expression and activation was accompanied by a defect in septum formation between mother and daughter cells. cDNA microarray analysis revealed 4 genes (CTS1, DSE1, DSE2, and SVS1) that changed expression in both a PKCalpha- and phorbol ester-dependent manner. These findings were confirmed by quantitative real-time PCR. Three of these genes are involved in cell wall turnover and are regulated by a single transcription factor (Ace 2) that localizes to daughter cell nuclei after cytokinesis. Taken together, these observations suggest that expression and activation of bovine PKCalpha in yeast cells repress growth by inducing an accumulation of cells in G2/M, likely through an impairment of chromosome segregation, cytokinesis, and septum formation. Moreover, when these observations are taken in the context of previously published observations with various yeast null mutants, we propose that bovine PKCalpha may directly or indirectly activate a subunit of the PP2A phosphatase complex (cdc55), which is a component of the mitotic spindle checkpoint.

Published
2007
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