Project description:Introduction and Objectives: Optimizing targeted therapy in patients with metastatic renal cell carcinoma (RCC) would improve clinical outcomes but patient derived xenograft (PDX) models are lacking. We present a novel pre-clinical model that is superior to nude mice for accommodating RCC PDXs. This preclinical model implants RC PDXs into the chorioallantoic membrane (CAM) of avian embryos and is a patient-specific platform that could be advantageous for physicians in the future when deciding what treatment options are best for their patients. This drug panelling platform is rapid, cost-effective, and relies on the highly angiogenic CAM to support RCC PDXs. Methods: Commercial and patient derived RCC cell lines, were grown to full confluence and transduced to generate fluorescently labeled versions of each cell line. Cells were implanted into the CAM. Tumors were treated every two days by applying 10 μL (10 μM) of indicated drug onto the tumor onplant. The drugs that were paneled include Sunitinib, Sorafenib, Pazopanib, Axitinib and a vehicle treatment. After 7–8 days of incubation post-implantation, tumor take rate was determined by the presence of tumor growth in the CAM using a fluorescent stereoscope. Results: The highest tumor take rates were observed in the vehicle treatments of the embryos, ranging from 50–86%. Both commercial and primary cell lines saw a reduction in tumor take rate with the application of various anti-angiogenic drugs. Specifically, XP121 tumors were resistant to Sorafenib; 786-0, XP121; XP206 were resistant to Pazopanib; T258, XP121 were resistant to Sunitinib; and lastly, T258 tumors were resistant to Axitinib (Table 1). Conclusions: RCC PDXs onplanted in the CAM of avian embryos offer a robust and cost-effective platform to predict sensitivity/resistance to targeted therapies. When evaluating several patient-derived RCC cell lines, drug paneling revealed other alternative treatment options for these PDXs. More importantly, RCC PDXs that were shown to be Sunitinib-resistant in both the patient and in mouse-based PDXs, also produced the same resistance phenotype in the CAM.
Project description:Introduction and objectivesThe management of kidney stone disease has changed dramatically over the past 30 years. In particular, ureteroscopy (URS) has become a more efficacious procedure with less morbidity. As a result, based on physician surveys and reports from single centre series the rate of URS appears to have increased over time. However, large population-based evaluations to assess the changes over time in the surgical treatment of kidney stone disease have not been conducted. Our objective was to evaluate population-based trends in the use of extracorporeal shockwave lithotripsy (SWL), URS and percutaneous nephrolithotomy (PCNL) over the past 20 years, in Ontario.MethodsUsing the Ontario Health Insurance Plan physician claims database we conducted a population-based cross-section time series analysis by identifying all kidney stone treatments performed between July 1, 1991 and Dec. 31, 2010, in the province of Ontario. The primary endpoint was the proportion of all stone treatments represented by each modality, which was calculated for every 3-month block over the study period. Exponential smoothing models were utilized to assess for trends over time in the percent utilization of each of SWL, URS and PCNL.ResultsWe identified 194,781 kidney stone treatments between July 1, 1991 and Dec. 31, 2010. A total of 96,807 SWL treatments, 83,923 URS treatments and 14,051 PCNL treatments were performed. We observed a significant trend over time for decreased utilization of SWL (68.5% to 33.7%, p<0.0001) and an increase in URS utilization (24.6% to 59.5%, p=0.0002), while no change over time was found for PCNL (6.88% to 6.85%, p=0.97) (Fig. 1). By the end of 2004, URS had become the most widely used procedure.ConclusionsOur population-based study confirms the increased use of URS over time suggested by physician survey and single centre retrospective series. Accordingly, the utilization of SWL has decreased in a reciprocal fashion.
Project description:Sponsorship: Publication of this supplement was sponsored by the Association for the Study of Obesity (ASO). All content was reviewed and approved by the ASO Committee, which held full responsibility for the abstract selections.