Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments, and the administration of chemotherapeutic drugs is often accompanied by toxic side effects. Combination therapy is one tool that can be used to combat therapeutic resistance and drug toxicity. Vitamin E (VE) compounds and analogs have been proposed as potential non-toxic chemotherapeutics. Here we modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to determine whether combinations of three chemotherapeutic agents: γ-tocotrienol (γ-T3), α-tocopherol ether acetate (α-TEA), and docetaxel (DOC), would prove more effective than docetaxel alone in the treatment of human prostate cancer cells. Response surfaces were generated for cell viability, and the optimal treatment combination for reducing cell viability was calculated. We found that a combination of 20 µM γ-T3, 30 µM α-TEA, and 25 nm DOC was most effective in the treatment of PC-3 cells. We also found that the combination of γ-T3 and α-TEA with DOC decreased the amount of DOC required to reduce cell viability in PC-3 cells and ameliorated therapeutic resistance in DOC-resistant PC-3 cells.
Feed1st, a no-questions-asked, self-serve food pantry program at a Chicago, Illinois, medical center, increased its impact during the COVID-19 pandemic, adding five new pantries and distributing 124% more food in March 2020 to November 2021 (42 970 pounds or 36 000 meals) than in the same period of 2018 to 2019 (19 220 pounds or 16 000 meals). Of 11 locations, distribution was highest in a phlebotomy waiting area and a cafeteria pantry. The community-engaged model enabled Feed1st to increase food access for patients, caregivers, and workers during the pandemic. (Am J Public Health. Published online ahead of print August 25, 2022:e1–e5. https://doi.org/10.2105/AJPH.2022.306984 )
Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments. Moreover, the administration of conventional chemotherapeutic drugs, such as docetaxel (DOC), poses the risk of debilitating toxic side effects. Combination chemotherapy, in which several compounds targeting multiple cellular pathways are administered jointly, is one tool that can be used to combat therapeutic resistance and drug toxicity. Vitamin E (VE) compounds and analogs have been proposed as potential non‐toxic chemotherapeutics. We modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to determine whether combinations of three chemotherapeutic agents (γ‐tocotrienol (γ‐T3), α‐tocopherol ether acetate (α‐TEA), and DOC) would prove more effective than DOC alone in the treatment of PC‐3 and DU145 human prostate cancer cells. A response surface was generated for cell viability, and the optimal treatment combination for reducing PC‐3 cell viability was calculated. We found that a combination of 30 μM α‐TEA, 20 μM γ‐T3, and 25 nm DOC was most effective in the treatment of PC‐3 cells. We also found that combining γ‐T3 and α‐TEA with DOC decreased the dose of DOC required to significantly reduce cell viability in PC‐3 and DU145 cells. Further, combination treatment consisting of α‐TEA, γ‐T3, and DOC induced apoptosis in PC‐3 cells as evidenced by upregulation of caspases 3 and 7. Finally, we found that combining γ‐T3 and α‐TEA with DOC enhanced treatment efficacy in DOC‐resistant PC‐3 cells. Support or Funding Information Brigham Young University College Undergraduate Research AwardBryant Adams
Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments such as docetaxel. Chemotherapeutic resistance is one of the greatest challenges facing successful cancer treatment, but can be ameliorated with combination chemotherapy. Vitamin E analogs, such as γ‐tocotrienol (γ‐T3) and α‐tocopheryloxyacetic acid (α‐TEA), have been proposed and studied as potential chemotherapeutics. We modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to see if combinations of three chemotherapeutic agents (γ‐T3, α‐TEA, and docetaxel) would be better than docetaxel alone in the treatment of PC‐3 human prostate cancer cells. Response surfaces were generated for cell viability and apoptotic responses and the optimal treatment combination for each response was calculated. We found that a combination of γ‐tocotrienol, α‐TEA, and docetaxel was more effective than docetaxel alone in the treatment of PC‐3 cells, and docetaxel resistant PC‐3 cells.Support or Funding InformationThis work was funded by a generous donation from the Bryant Adams Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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