Renal adenocarcinoma is a common malignancy of adults which is poorly responsive to conventional chemotherapy. Glycosphingolipids are ubiquitous and complex glycocongugates which have been implicated in the growth and differentiation of many types of malignancies. The recent development and application of specific inhibitors of glycolipid metabolism, as well as homologously related compounds, by the investigators provides a novel and potentially useful approach to the treatment of this cancer possibly through inhibition of metastasis. We propose to study the functional roles played by glycosphingolipids in the growth of renal adenocarcinoma and evaluate the potential treatment of renal cell carcinoma by the inhibition of glycosphingolipid synthesis. The following questions are to be addressed in this proposal. What are the effects of inhibition of glucosylceramide synthase by 1- phenyl-2-decanoylamino-3-morpholino-1-propanol, beta-glucosidase by conduritol B epoxide, and of 3-ketodihydrosphingosine synthase by cycloserine on the growth of cultured renal adenocarcinoma cells? What is the role of protein kinase C activity in mitogen stimulated renal cell carcinoma proliferation? Is the inhibition of growth resulting from glucosylceramide synthase inhibition mediated by changes in protein kinase C? Is the inhibition of growth mediated by changes in cellular adherence to extracellular matrix proteins? What are the growth characteristics of renal adenocarcinoma cells implanted in mice which are then treated with glucosylceramide synthase inhibitors?
| Hato, Takashi; Winfree, Seth; Day, Richard et al. (2017) Two-Photon Intravital Fluorescence Lifetime Imaging of the Kidney Reveals Cell-Type Specific Metabolic Signatures. J Am Soc Nephrol 28:2420-2430 |
| Kikuchi, Masao; Wickman, Larysa; Hodgin, Jeffrey B et al. (2015) Podometrics as a Potential Clinical Tool for Glomerular Disease Management. Semin Nephrol 35:245-55 |
| Yu, Fa-Xing; Zhao, Bin; Guan, Kun-Liang (2015) Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell 163:811-28 |
| Fukuda, Akihiro; Wickman, Larysa T; Venkatareddy, Madhusudan P et al. (2012) Urine podocin:nephrin mRNA ratio (PNR) as a podocyte stress biomarker. Nephrol Dial Transplant 27:4079-87 |
| Fukuda, Akihiro; Wickman, Larysa T; Venkatareddy, Madhusudan P et al. (2012) Angiotensin II-dependent persistent podocyte loss from destabilized glomeruli causes progression of end stage kidney disease. Kidney Int 81:40-55 |
| Wiggins, Jocelyn E (2012) Aging in the glomerulus. J Gerontol A Biol Sci Med Sci 67:1358-64 |
| Fukuda, Akihiro; Chowdhury, Mahboob A; Venkatareddy, Madhusudan P et al. (2012) Growth-dependent podocyte failure causes glomerulosclerosis. J Am Soc Nephrol 23:1351-63 |
| Chernin, Gil; Vega-Warner, Virginia; Schoeb, Dominik S et al. (2010) Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations. Clin J Am Soc Nephrol 5:1655-62 |
| Chernin, Gil; Heeringa, Saskia F; Vega-Warner, Virginia et al. (2010) Adequate use of allele frequencies in Hispanics--a problem elucidated in nephrotic syndrome. Pediatr Nephrol 25:261-6 |
| Kim, Doyeob; Patel, Sanjeevkumar R; Xiao, Hong et al. (2009) The role of PTIP in maintaining embryonic stem cell pluripotency. Stem Cells 27:1516-23 |
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