Vol. 179, No. 4, Supplement, Sunday, May 18, 2008 THE JOURNAL OF UROLOGY ® 35 with Sunitinib inhibited cell progression regulator c-Myc phosphorylation and expression in a dose dependent manner, but Sunitinib alone did decreased Cyclin D1 expression with the combination producing better dose dependent inhibition. Sunitinib inhibited VEGF secretion through normoxia and hypoxia conditions in a dose dependent fashion, and CONCLUSIONS: Targeting Src kinase and RTKs reduction of acquired drug resistance in Caki-1. This combination strategy may hold clinical promise. Source of Funding: UC Davis. 98 NOVEL SN-38-INCORPORATED POLYMERIC MICELLES, NK012, ERADICATE LUNG METASTASES AND INCREASE SURVIVAL IN THE MURINE RENAL CANCER MODEL Makoto Sumitomo*, Fumiaki Koizumi, Takako Asano, Akio Horiguchi, Keiichi Ito, Tomohiko Asano, Yasuhiro Matsumura, Tadao Kakizoe, Masamichi Hayakawa. Tokorozawa, Saitama, Japan, Tokyo, Japan, and Chiba, Japan. INTRODUCTION AND OBJECTIVE: It has been recently shown that NK012, a 7-ethyl-10-hydroxy-camptothecin (SN-38) releasing nano-device, possesses potent antitumor activities especially in hypervascular tumors such as renal cell carcinoma (RCC) through the enhanced permeability and retention effect. We studied the drug distribution and antitumor activity of NK012 using established RCC tumor models with pulmonary metastases being frequently found in patients with disseminated RCCs. METHODS: The animal experimental protocols were conducted in accordance with the Guidelines for Animal Experiments in the National Cancer Center. The treatment was initiated 7 days after intravenous inoculation of the murine Renca cells in BALB/c mice (day 0), when multiple lung nodules (126 ± 23 nodules, n = 10) derived from Renca were observed. NK012 (20 mg/kg/day) and CPT-11 (30 mg/kg/day) were administered intravenously on day 0, 4, and 8. The and the concentration of free SN-38 in the lung was determined using the high-performance liquid chromatography method. Other mice were maintained until each animal showed signs of severe morbidity after treatment. Kaplan-Meier analysis was done to determine the effect on time to morbidity. RESULTS: After the NK012 administration, free SN-38 was stably detectable at the concentration of >100 ng/g in metastatic lung P the mean number of metastatic nodules in the control group (287 ± 56 nodules, n = 10) and that in the CPT-11 treatment group (236 ± 59 nodules, n nodules was observed, however, in theNK012 treatment group (32 ± 18 nodules, n = 10) compared with the control group (P < 0.001, Figure). obtained in the NK012 treatment group (P < 0.001) but not in the CPT-11 treatment group (P = 0.239) as compared with the control group. CONCLUSIONS: Our study suggests the advantage of polymeric micelle-based drug carriers like NK012 especially as promising modalities for the treatment of disseminated RCCs. Source of Funding: None 99 SUPPRESSION OF RENAL CELL CARCINOMA GROWTH AND METASTASIS WITH SUSTAINED ANTIANGIOGENIC GENE THERAPY Matthew J Mellon*, Kyung-Hee Bae, Catherine E Steding, Chinghai Kao, Thomas A Gardner. Indianapolis, IN. INTRODUCTION AND OBJECTIVE: Renal Cell Carcinoma (RCC) is the third most common urologic neoplasm. This aggressive malignancy has proven refractory to conventional treatment options. Recently, antiangiogenic agents have shown early success in treating metastatic disease. The highly vascular nature of RCC appears particularly susceptible to this approach. This study investigates the potential of sustained expression of an endostatin-angiostatin fusion protein in an early-stage model of RCC to inhibit tumor growth and metastasis. METHODS: Subcutaneous RCC-29 tumors were induced in 7-week old athymic nude male mice by injecting 2x10 6 cells bilaterally into each flank region. Mice were divided into two groups. Once tumors reached volumes of 10 mm 3 and 25 mm 3 respectively, subjects adenoviral vector every 20 days until the conclusion of the trial. The mice were randomly assigned to three treatment groups: saline control, viral Ad-GFP control and Ad-EndoAngio, encoding a chimeric endostatin- angiostatin fusion protein. Tumor volumes were measured twice weekly for 80 days. During days 40-50 of the trial, subjects were administered imaging of the tumor vasculature to ascertain angiogenic changes. All animals underwent post-mortem histopathogical analysis to assess for metastatic disease in the kidney, lung, liver, brain and spleen. RESULTS: The 10 mm 3 and 25 mm 3 tumor arms when treated with Ad-EndoAngio displayed 97% and 92% growth reduction respectively (p<0.001) as compared to saline and viral controls. Further, in vivo tumor vascular imaging illustrated a reduction in blood vessel number and Ad-EndoAngio treatment. Importantly, histopathological examination demonstrated marked lung and liver metastases suppression in the treatment arms as compared to controls. CONCLUSIONS: These results suggest that sustained EndoAngio gene therapy has effective antiangiogenic action against human RCC tumors and possesses potential as a novel treatment for metastatic renal cell carcinoma. Source of Funding: This study was supported by NIH/ NIDDK P50 DK061594-03 (TAG), DOD DAMD 17-03-1-0077 (TAG), NIH R01 CA80825-01A2 (CK), and NIH T32 CA111198 (MJM). 100 PROTEOMIC IDENTIFICATION AND VALIDATION OF INTERLEUKIN-2 THERAPY RESPONSE IN METASTATIC RENAL CELL CANCER Jon Jones*, Hasan H Otu, Dimitrios Spentzos, Arie S Belldegrun, Towia A Libermann, Allan J Pantuck. Boston, MA, and Los Angeles, CA. INTRODUCTION AND OBJECTIVE: To detect a predictive