RCC accounts for 9 out of 10 cases of kidney cancer. Approximately 65,150 new cases and 13,680 deaths are expected from this disease in 2013. There is urgent clinical need for better treatment options as RCC responds poorly to current chemotherapy. A major limitation to developing new treatments is that the molecular mechanisms responsible for inappropriate cell survival and chemoresistance are unknown. One pathway suggested to be involved in vitro is the JAK2/STAT. We hypothesized that there would be altered expression of the members and regulators of the JAK/STAT pathways in RCC. We utilized samples from normal (n=14), benign (n=6), and histological Fuhrman grades: Grade 1 (n=3), Grade 2 (n=10), Grade 3 (n=14), and Grade 4 (n=3). We analyzed 31 human RCC samples as well as the normal and benign samples with Affymetrix human gene microarrays and Western Blot technology. The samples were all clear cell renal carcinomas verified by a Beaumont Hospital pathologist. We analyzed 22,148 genes and altered gene expression was then detected by ANOVA taking into account histological stage. We found 170 genes that were differentially expressed in all grades compared to both normal and benign kidney samples. We found both JAK1 and JAK2 mRNA to be highly expressed in the RCC samples compared to the controls. We did not observe any decrease in the mRNA levels or protein expression of the regulatory proteins SOCS1, SOCS3 or SHP‐1. We did find an increase in SHP‐1 serine phosphorylation which is inhibitory in the RCC samples. These data suggest that altered function of the regulators not expression may be involved in RCC.
Grant Funding Source: Zafarna Foundation
Many researchers have utilized submerged jet impingement geometry to study solid particle erosion/corrosion. However, only a few studies have investigated changing impingement angle and fluid viscosity. In this study, Particle Image Velocimetry (PIV) experiments were conducted using 14 micron glass spheres for direct impingement geometry at viscosities of 1, 14, and 55 cP. These viscosities correspond to Reynolds numbers of approximately 57000, 4000, and 1000, respectively. It was observed that by increasing the viscosity the flow exiting the nozzle transitioned from extremely turbulent to laminar flow. The data indicated fully turbulent flow at the outlet for viscosities of 1 and 14 cP. In the case of 55 cP flow, the flow exiting the nozzle became laminar contributing to a higher maximum velocity in 55 cP flow. Experiments at these viscosities were also conducted at impingement angles of 90, 75, and 45 degrees to investigate the effects of the impinging jet angle on a flat plate. Additionally, a series of Computational Fluid Dynamics (CFD) simulations of the flowfield were performed to compare with the experimental data collected in this paper.
There is urgent clinical need for better treatment options as RCC responds poorly to chemotherapy and currently has no early detection biomarkers available. We previously demonstrated increased activity of Janus Kinase (JAK2) pathway.We hypothesized that increased JAK2 activity resulted in increased levels of MAP7, linked to chemoresistance, and decreased levels of Uromodulin, a secreted protein linked to renal protection, measurable in the urine. We utilized samples from normal (n=14), benign (n=6), and histological Fuhrman grades: Grade 1 (n=3), Grade 2 (n=10), Grade 3 (n=14), and Grade 4 (n=3). We analyzed samples with Affymetrix human gene microarrays and Western Blot technology. The samples were all clear cell renal carcinomas verified by a pathologist. Altered gene and protein expression was detected by ANOVA taking into account histological stage. We found MAP7 mRNA to be highly expressed in the RCC samples compared to the controls and benign and it increased with severity of the cancer stage. Uromodulin mRNA levels were increased in the benign samples compared to control and were undetectable in all stages of the RCC samples. We saw corresponding changes in the protein levels of both MAP7 and Uromodulin. We also performed an ELISA to measure Uromodulin in the urine and found a significant decreases in stage 3 and 4 RCC samples compared to normal and benign. There were significant increases in Uromodulin in benign, stage 1 and 2 RCC samples compared to control. These data suggest that altered function of these protein may be involved in RCC. Zafarna Fund
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