The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
Problem: The prospect that urban heat island (UHI) effects and climate change may increase urban temperatures is a problem for cities that actively promote urban redevelopment and higher densities. One possible UHI mitigation strategy is to plant more trees and other irrigated vegetation to prevent daytime heat storage and facilitate nighttime cooling, but this requires water resources that are limited in a desert city like Phoenix.
Purpose: We investigated the tradeoffs between water use and nighttime cooling inherent in urban form and land use choices.
Methods: We used a Local-Scale Urban Meteorological Parameterization Scheme (LUMPS) model to examine the variation in temperature and evaporation in 10 census tracts in Phoenix's urban core. After validating results with estimates of outdoor water use based on tract-level city water records and satellite imagery, we used the model to simulate the temperature and water use consequences of implementing three different scenarios.
Results and conclusions: We found that increasing irrigated landscaping lowers nighttime temperatures, but this relationship is not linear; the greatest reductions occur in the least vegetated neighborhoods. A ratio of the change in water use to temperature impact reached a threshold beyond which increased outdoor water use did little to ameliorate UHI effects.
Takeaway for practice: There is no one design and landscape plan capable of addressing increasing UHI and climate effects everywhere. Any one strategy will have inconsistent results if applied across all urban landscape features and may lead to an inefficient allocation of scarce water resources.
Research Support: This work was supported by the National Science Foundation (NSF) under Grant SES-0345945 (Decision Center for a Desert City) and by the City of Phoenix Water Services Department. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of NSF.
This study addresses a classic sustainability challenge—the tradeoff between water conservation and temperature amelioration in rapidly growing cities, using Phoenix, Arizona and Portland, Oregon as case studies. An urban energy balance model— LUMPS (Local-Scale Urban Meteorological Parameterization Scheme)—is used to represent the tradeoff between outdoor water use and nighttime cooling during hot, dry summer months. Tradeoffs were characterized under three scenarios of land use change and three climate-change assumptions. Decreasing vegetation density reduced outdoor water use but sacrificed nighttime cooling. Increasing vegetated surfaces accelerated nighttime cooling, but increased outdoor water use by ~20%. Replacing impervious surfaces with buildings achieved similar improvements in nighttime cooling with minimal increases in outdoor water use; it was the most water-efficient cooling strategy. The fact that nighttime cooling rates and outdoor water use were more sensitive to land use scenarios than climate-change simulations suggested that cities can adapt to a warmer climate by manipulating land use.