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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.
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The United States’ War on Drugs declared in 1971 by President Richard Nixon and revamped by President Reagan in the 1980s has been an objectively failed initiative with origins based in racism and oppression. After exploring the repercussions of this endeavor for societies and individuals around the world, global researchers and policymakers have declared that the policies and institutions created to fight the battle have left devastation in their wake. Despite high economic and social costs, missed opportunities in public health and criminal justice sectors, and increasing limits on our personal freedoms, all the measures taken to eradicate drug abuse and trafficking have been unsuccessful. Not only that, but militarized police tactics, mass incarceration, and harsh penalties that stifle opportunities for rehabilitation, growth, and change disproportionately harm poor and minority communities. <br/>Because reform in U.S. drug policy is badly needed, the goals of America’s longest war need to be reevaluated, implications of the initiative reexamined, and alternative strategies reconsidered. Solutions must be propagated from a diverse spectrum of contributors and holistic understanding through scientific research, empirical evidence, innovation, public health, social wellbeing, and measurable outcomes. But before we can know where we should be headed, we need to appreciate how we got to where we are. This preliminary expository investigation will explore and outline the history of drug use and prohibition in the United States before the War on Drugs was officially declared. Through an examination of the different patterns of substance use, evolving civil tolerance of users, racially-charged anti-drug misinformation/propaganda campaigns, and increasingly restrictive drug control policies, a foundation for developing solutions and strengths-based strategies for drug reform will emerge.