- Email: [email protected]
293 PREVENTION AND INHIBITION OF TUMOR GROWTH BY CHOLECALCIFEROL IN RENAL CELL CARCINOMA
Vol. 187, No. 4S, Supplement, Sunday, May 20, 2012
estimated at $500 initial charge and $30 for each subsequent minute. Hence, the cost of a routine SWL and URS (assuming 30 min surgery time) are approximately $2,292.1 and $1,856.2, respectively. CONCLUSIONS: Our single urologist experience (GP) with stones less than 1.5 cm in diameter reveal superior SFR for URS. Our cost analysis also reveals that URS is less expensive than SWL, particularly in light of cost of subsequent procedures needed in SWL. With the implementation of accountable care systems, SWL may become a poor initial choice for upper urinary calculi. Furthermore, the impact on lithotripsy partnerships, which depend on stone volume for revenue, may be detrimental. Source of Funding: None
292 THE USE OF ADJUVANT RADIATION THERAPY IN STAGE I SEMINOMA AND ITS EFFECT ON SURVIVAL Christopher Deibert*, Max Kates, Beverly J Insel, Israel Deutsch, James M McKiernan, Benjamin A. Spencer, New York, NY INTRODUCTION AND OBJECTIVES: To assess differences in overall and testis cancer-specific survival among patients with stage I seminoma treated with and without radiation therapy (RT). METHODS: We selected 10,968 patients from the Surveillance, Epidemiology and End Results database with histologically-confirmed Stage I seminoma diagnosed from 1990-2007 who were treated with radical orchiectomy. Multivariate logistic regression was used to predict the odds of undergoing RT. The association between RT and overall and testis cancer-specific survival, were compared, adjusting for patient and tumor characteristics. RESULTS: Overall, 70% (7,710) of the analytic cohort underwent adjuvant RT. The use of RT decreased incrementally during the study period, from 79% in 1990 to 53% in 2007. We found two predictors of undergoing RT: being married (OR: 1.41; 95%CI 1.301.55 vs. single/divorced/widowed) and T2 disease (OR: 1.14; 95% CI 1.01-1.27 vs. T1). Hispanic ethnicity decreased the likelihood of RT (OR: 0.86; 95% CI 0.76-0.97). After controlling for patient and tumor characteristics, RT was a significant predictor of improved overall survival (HR: 0.52; 95%CI 0.42-0.64) and improved testis cancerspecific survival (HR: 0.38; 95%CI 0.0.22-0.63). CONCLUSIONS: The use of adjuvant RT following radical orchiectomy for stage I seminoma has fallen to slightly more than half of patients. Our study demonstrates that RT in this setting is associated with improved overall and testis cancer-specific survival compared with no treatment. With current guidelines advocating surveillance for this disease setting, additional prospective studies to better quantify the risks and benefits of adjuvant radiation are warranted.
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factors acting normally during renal development are reactivated during renal tumorigenesis, it is the case for the Hedgehog (HH) pathway, the Wnt signaling and some transcription factors like Lim1 or Pax2/8. On the one hand, it has been recently demonstrated that HH signaling contributes to RCC growth; on the other hand, a precursor of the active vitamin D3, cholecalciferol, is a strong inhibitor of the HH signaling. Here we characterize and analyze the effects of cholecalciferol in this refractory disease. METHODS: A panel of conventional RCC (CCC) cell lines expressing or not the von Hippel-Lindau tumor suppressor gene as well as tumors and normal corresponding tissues from CCC patients were used. The expression of the vitamin D3 signaling pathway components were investigated by RT-PCR and Western blot. The effects of vitamin D3 compounds on cell proliferation and cell death were analyzed by cell counting, BrdU incorporation studies, and FACS analysis respectively. The activation status of the tumorigenic signaling pathways PI3K/Akt, NF-kB and MAPK, as well as other markers involved in apoptosis, angiogenesis and migration was measured by Western blot and proteome arrays. Human CCC tumor-bearing nude mice were treated both in a therapeutic and prophylactic manner. Tumor proliferation, death and vascularization were measured by Ki67, TUNEL and CD40 staining, respectively. Calcium reabsorption, calcification and vitamin D3 metabolites concentrations were monitored during the experiments. RESULTS: We confirmed that vitamin D3 components are not expressed in the tumoral kidney. We showed that cholecalciferol decreases cell proliferation, increases necrosis in CCC cell lines through inhibition of the HH pathway, and does not interfere with the growth of normal renal cells. Xenografted mice treated with cholecalciferol in a prophylactic or a therapeutic manner present absence of tumor development or substantial growth inhibition. In addition, the treatment is very safe because it does not induce calcification or calcium reabsorption. CONCLUSIONS: Here we demonstrated that even if the components of the vitamin D3 metabolism are no more present in CCC, cholecalciferol supplementation might be a very strong tool to block the HH pathway reactivated in this pathology, with ultimate tumor regression. All together, these findings reveal that cholecalciferol may have highly therapeutic potential against human CCC. Source of Funding: This study was sponsored by INSERM (Institut National de la Sante´ Et de la Recherche Me´dicale), University of Strasbourg and the French Ligue Contre le Cancer (Comite´s du Bas-Rhin et du Haut-Rhin et Comite´ National, recipient TM).
294 INCOMPLETE THERMAL ABLATION INDUCES INCREASED PROLIFERATION OF RENAL CARCINOMA CELLS IN A MURINE MODEL.
Source of Funding: None
Kidney Cancer: Basic Research II Moderated Poster Sunday, May 20, 2012
THE JOURNAL OF UROLOGY姞
10:30 AM-12:30 PM
293 PREVENTION AND INHIBITION OF TUMOR GROWTH BY CHOLECALCIFEROL IN RENAL CELL CARCINOMA Vale´rian Dormoy*, Claire Be´raud, Strasbourg, France, Metropolitan; Ve´ronique Lindner, Mulhouse, France, Metropolitan; Catherine Coquard, David Brasse, Didier Jacqmin, Herve´ Lang, Thierry Massfelder, Strasbourg, France, Metropolitan INTRODUCTION AND OBJECTIVES: Human renal cell carcinoma (RCC) remains resistant to the conventional treatments despite the progress in therapies. Several signaling pathways and transcription
Stephanie Kroeze, Utrecht, Netherlands; Harm van Melick*, Nieuwegein, Netherlands; Maarten Nijkamp, Laura Kruijssen, Paul van Diest, Ruud Bosch, Judith Jans, Utrecht, Netherlands INTRODUCTION AND OBJECTIVES: Local recurrences of renal tumors occur frequently after radiofrequency ablation (RFA) and cryoablation (CA), and are observed more often compared to partial nephrectomy (PN). Although these high recurrence rates may be partly due to incomplete tumour ablation, stimulatory factors triggered by the thermal ablation could contribute to increased growth of surviving tumor cells. The aim of this study was to compare the presence of cell proliferation and stimulatory factors for growth and survival in renal tumors following RFA, CA and PN. METHODS: Renca renal tumors were orthotopically transplanted under the renal capsule of mice (4-6 mice/group), and RFA, CA or PN was performed. Tumors were ablated incompletely (RFA and CA) or a part of the tumor was left behind (PN). At several time points (2h and 1, 3, 7, 14 days) hereafter, presence of cell proliferation (Ki67), hypoxia, inflammatory factors (CD45, F4/80) and the heat shock proteins (HSP70 and HSP90) was evaluated using immunohistochemistry.
estimated at $500 initial charge and $30 for each subsequent minute. Hence, the cost of a routine SWL and URS (assuming 30 min surgery time) are approximately $2,292.1 and $1,856.2, respectively. CONCLUSIONS: Our single urologist experience (GP) with stones less than 1.5 cm in diameter reveal superior SFR for URS. Our cost analysis also reveals that URS is less expensive than SWL, particularly in light of cost of subsequent procedures needed in SWL. With the implementation of accountable care systems, SWL may become a poor initial choice for upper urinary calculi. Furthermore, the impact on lithotripsy partnerships, which depend on stone volume for revenue, may be detrimental. Source of Funding: None
292 THE USE OF ADJUVANT RADIATION THERAPY IN STAGE I SEMINOMA AND ITS EFFECT ON SURVIVAL Christopher Deibert*, Max Kates, Beverly J Insel, Israel Deutsch, James M McKiernan, Benjamin A. Spencer, New York, NY INTRODUCTION AND OBJECTIVES: To assess differences in overall and testis cancer-specific survival among patients with stage I seminoma treated with and without radiation therapy (RT). METHODS: We selected 10,968 patients from the Surveillance, Epidemiology and End Results database with histologically-confirmed Stage I seminoma diagnosed from 1990-2007 who were treated with radical orchiectomy. Multivariate logistic regression was used to predict the odds of undergoing RT. The association between RT and overall and testis cancer-specific survival, were compared, adjusting for patient and tumor characteristics. RESULTS: Overall, 70% (7,710) of the analytic cohort underwent adjuvant RT. The use of RT decreased incrementally during the study period, from 79% in 1990 to 53% in 2007. We found two predictors of undergoing RT: being married (OR: 1.41; 95%CI 1.301.55 vs. single/divorced/widowed) and T2 disease (OR: 1.14; 95% CI 1.01-1.27 vs. T1). Hispanic ethnicity decreased the likelihood of RT (OR: 0.86; 95% CI 0.76-0.97). After controlling for patient and tumor characteristics, RT was a significant predictor of improved overall survival (HR: 0.52; 95%CI 0.42-0.64) and improved testis cancerspecific survival (HR: 0.38; 95%CI 0.0.22-0.63). CONCLUSIONS: The use of adjuvant RT following radical orchiectomy for stage I seminoma has fallen to slightly more than half of patients. Our study demonstrates that RT in this setting is associated with improved overall and testis cancer-specific survival compared with no treatment. With current guidelines advocating surveillance for this disease setting, additional prospective studies to better quantify the risks and benefits of adjuvant radiation are warranted.
e119
factors acting normally during renal development are reactivated during renal tumorigenesis, it is the case for the Hedgehog (HH) pathway, the Wnt signaling and some transcription factors like Lim1 or Pax2/8. On the one hand, it has been recently demonstrated that HH signaling contributes to RCC growth; on the other hand, a precursor of the active vitamin D3, cholecalciferol, is a strong inhibitor of the HH signaling. Here we characterize and analyze the effects of cholecalciferol in this refractory disease. METHODS: A panel of conventional RCC (CCC) cell lines expressing or not the von Hippel-Lindau tumor suppressor gene as well as tumors and normal corresponding tissues from CCC patients were used. The expression of the vitamin D3 signaling pathway components were investigated by RT-PCR and Western blot. The effects of vitamin D3 compounds on cell proliferation and cell death were analyzed by cell counting, BrdU incorporation studies, and FACS analysis respectively. The activation status of the tumorigenic signaling pathways PI3K/Akt, NF-kB and MAPK, as well as other markers involved in apoptosis, angiogenesis and migration was measured by Western blot and proteome arrays. Human CCC tumor-bearing nude mice were treated both in a therapeutic and prophylactic manner. Tumor proliferation, death and vascularization were measured by Ki67, TUNEL and CD40 staining, respectively. Calcium reabsorption, calcification and vitamin D3 metabolites concentrations were monitored during the experiments. RESULTS: We confirmed that vitamin D3 components are not expressed in the tumoral kidney. We showed that cholecalciferol decreases cell proliferation, increases necrosis in CCC cell lines through inhibition of the HH pathway, and does not interfere with the growth of normal renal cells. Xenografted mice treated with cholecalciferol in a prophylactic or a therapeutic manner present absence of tumor development or substantial growth inhibition. In addition, the treatment is very safe because it does not induce calcification or calcium reabsorption. CONCLUSIONS: Here we demonstrated that even if the components of the vitamin D3 metabolism are no more present in CCC, cholecalciferol supplementation might be a very strong tool to block the HH pathway reactivated in this pathology, with ultimate tumor regression. All together, these findings reveal that cholecalciferol may have highly therapeutic potential against human CCC. Source of Funding: This study was sponsored by INSERM (Institut National de la Sante´ Et de la Recherche Me´dicale), University of Strasbourg and the French Ligue Contre le Cancer (Comite´s du Bas-Rhin et du Haut-Rhin et Comite´ National, recipient TM).
294 INCOMPLETE THERMAL ABLATION INDUCES INCREASED PROLIFERATION OF RENAL CARCINOMA CELLS IN A MURINE MODEL.
Source of Funding: None
Kidney Cancer: Basic Research II Moderated Poster Sunday, May 20, 2012
THE JOURNAL OF UROLOGY姞
10:30 AM-12:30 PM
293 PREVENTION AND INHIBITION OF TUMOR GROWTH BY CHOLECALCIFEROL IN RENAL CELL CARCINOMA Vale´rian Dormoy*, Claire Be´raud, Strasbourg, France, Metropolitan; Ve´ronique Lindner, Mulhouse, France, Metropolitan; Catherine Coquard, David Brasse, Didier Jacqmin, Herve´ Lang, Thierry Massfelder, Strasbourg, France, Metropolitan INTRODUCTION AND OBJECTIVES: Human renal cell carcinoma (RCC) remains resistant to the conventional treatments despite the progress in therapies. Several signaling pathways and transcription
Stephanie Kroeze, Utrecht, Netherlands; Harm van Melick*, Nieuwegein, Netherlands; Maarten Nijkamp, Laura Kruijssen, Paul van Diest, Ruud Bosch, Judith Jans, Utrecht, Netherlands INTRODUCTION AND OBJECTIVES: Local recurrences of renal tumors occur frequently after radiofrequency ablation (RFA) and cryoablation (CA), and are observed more often compared to partial nephrectomy (PN). Although these high recurrence rates may be partly due to incomplete tumour ablation, stimulatory factors triggered by the thermal ablation could contribute to increased growth of surviving tumor cells. The aim of this study was to compare the presence of cell proliferation and stimulatory factors for growth and survival in renal tumors following RFA, CA and PN. METHODS: Renca renal tumors were orthotopically transplanted under the renal capsule of mice (4-6 mice/group), and RFA, CA or PN was performed. Tumors were ablated incompletely (RFA and CA) or a part of the tumor was left behind (PN). At several time points (2h and 1, 3, 7, 14 days) hereafter, presence of cell proliferation (Ki67), hypoxia, inflammatory factors (CD45, F4/80) and the heat shock proteins (HSP70 and HSP90) was evaluated using immunohistochemistry.