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Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
In the last decade, the Climate Limited-area Modeling Community (CLM-Community) has contributed to the Coordinated Regional Climate Downscaling Experiment (CORDEX) with an extensive set of regional climate simulations. Using several versions of the COSMO-CLM-Community model, ERA-Interim reanalysis and eight global climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were dynamically downscaled with horizontal grid spacings of 0.44∘ (∼ 50 km), 0.22∘ (∼ 25 km), and 0.11∘ (∼ 12 km) over the CORDEX domains Europe, South Asia, East Asia, Australasia, and Africa. This major effort resulted in 80 regional climate simulations publicly available through the Earth System Grid Federation (ESGF) web portals for use in impact studies and climate scenario assessments. Here we review the production of these simulations and assess their results in terms of mean near-surface temperature and precipitation to aid the future design of the COSMO-CLM model simulations. It is found that a domain-specific parameter tuning is beneficial, while increasing horizontal model resolution (from 50 to 25 or 12 km grid spacing) alone does not always improve the performance of the simulation. Moreover, the COSMO-CLM performance depends on the driving data. This is generally more important than the dependence on horizontal resolution, model version, and configuration. Our results emphasize the importance of performing regional climate projections in a coordinated way, where guidance from both the global (GCM) and regional (RCM) climate modeling communities is needed to increase the reliability of the GCM–RCM modeling chain.
In the last decade, the Climate Limited-area Modeling (CLM) Community has contributed to the Coordinated Regional Climate Downscaling Experiment (CORDEX) with an extensive set of regional climate simulations. Using several versions of the COSMO-CLM community model, ERA-Interim reanalysis and eight Global Climate Models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were dynamically downscaled with horizontal grid spacings of 0.44◦(∼50 km), 0.22◦ (∼25 km) and 0.11◦ (∼12 km) over the CORDEX domains Europe, South Asia, East Asia, Australasia and Africa. This major effort resulted in 80 regional climate simulations publicly available through the Earth System Grid Federation (ESGF) web portals for use in impact studies and climate scenario assessments. Here we review the production of these simulations and assess their results in terms of mean near-surface temperature and precipitation to aid the future design of the COSMO-CLM model simulations. It is found that a domain-specific parameter tuning is beneficial, while increasing horizontal model resolution (from 50 to 25 or 12 km grid spacing) alone does not always improve the performance of the simulation. Moreover, the COSMO-CLM performance depends on the driving data. This is generally more important than the dependence on horizontal resolution, model version and configuration. Our results emphasize the importance of performing regional climate projections in a coordinated way, where guidance from both the global (GCM) and regional (RCM) climate modelling communities is needed to increase the reliability of the GCM-RCM modelling chain.