71 MOLECULAR TARGETS IN KIDNEY CANCER (2010)

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 201071 MOLECULAR TARGETS IN KIDNEY CANCER Andrew Chi, Samir Shirodkar, Miguel Gosalbez, Vincent Bird, Mohamed Aziz, John Sheilds, Mark Soloway, and Vinata Lokeshwar Andrew ChiAndrew Chi More articles by this author , Samir ShirodkarSamir Shirodkar More articles by this author , Miguel GosalbezMiguel Gosalbez More articles by this author , Vincent BirdVincent Bird More articles by this author , Mohamed AzizMohamed Aziz More articles by this author , John SheildsJohn Sheilds More articles by this author , Mark SolowayMark Soloway More articles by this author , and Vinata LokeshwarVinata Lokeshwar More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.119AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastatic kidney cancer is lethal because conventional treatments have poor response rates. Identification of new therapeutic targets and prognostic markers should lead to individualized treatments for this disease. We evaluated the expression of hyaluronidase family (HYAL1, HYAL2, HYAL4, HYALP1), hyaluronic acid synthase family (HAS1, HAS2, HAS3), hyaluronic acid receptors (RHAMM, CD44S, CD44v), inflammatory cytokine receptors (CXCR4, CXCR7) and chemokines (OPN) in tumor and matched normal tissues from patients with kidney cancer. METHODS Tumor and normal tissues were collected from kidney cancer patients undergoing nephrectomy (n=75; oncocytoma, 4; T1a or T1b, 33; T2+, 38; Grade 1, 5; Grade 2, 28; Grade 3, 23; Grade 4, 15). RNA isolated from tissues was subjected to real time RT-PCR for 14 markers: HYAL1, HYAL2, HYAL4, HYAL-P1, HAS1, HAS2, HAS3, IL-8, OPN, CXCR4, CXCR7, RHAMM, CD44st, and CD44v. For normalization, real time PCR was performed for 18S, â-actin, PPIA v1, PPIA v4, TBP. RESULTS Except TBP (Tata Binding Protein), levels of 18S, B-actin, PPIA v1, PPIA v4 mRNAs were elevated in tumor tissues (P < 0.01; t-test). Therefore, the levels of all 14 markers were normalized to TBP. Among the 14 markers, CXCR7 (tumor: 1295 +/- 3673; normal: 514 +/- 896; P < 0.0001), CXCR4 (tumor: 2479 +/- 2262; normal: 1122 +/- 1307; P < 0.0001), RHAMM (tumor: 18.56 +/- 20.44; normal: 3.235 +/- 3.721; P < 0.0001), and CD44S (tumor: 480.7 +/- 684.6; normal: 126.5 +/- 114; P < 0.0001) levels were higher in tumor, when compared to normal tissues. CONCLUSIONS This study identifies RHAMM, CXCR7, CXCR4, and CD44S are molecules likely to be associated with the pathophysiology of kidney cancer. Furthermore, TBP is a better standard for normalization in real time PCR assays and matched tumor and normal specimens help in discovering novel cancer biomarkers and treatment targets. Miami, FL© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e30 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Chi More articles by this author Samir Shirodkar More articles by this author Miguel Gosalbez More articles by this author Vincent Bird More articles by this author Mohamed Aziz More articles by this author John Sheilds More articles by this author Mark Soloway More articles by this author Vinata Lokeshwar More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...