Browsing by Subject "Epithelial-Mesenchymal Transition"
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Item Analysis of Key Cellular Changes of Triple Negative Breast Cancer Cells in Response to Kinase-Inhibiting BI2536 and Associated Derivatives(2023-05) Baker, Christopher V.; Bunnell, Bruce A.; Burow, Matthew; Chaudhary, PankajPurpose: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer that grows quickly and has higher rates of metastasis and reoccurrence relative to other Breast Cancer subtypes that make it, in general, a much more dangerous subtype of breast cancer. The Kinase Chemogenomic Set (KCGS) is a collection of 187 kinase-inhibiting compounds with broad activity across 215 different kinases. We hypothesize that this plate contains compounds with the potential to inhibit TNBC and that exploring the transcriptomic and proteomic changes in TNBC cells may give insights into novel treatment targets. Methods: To test this hypothesis, we have utilized two main cell lines, the MDA-MB-231 line and a patient-derived xenograft line, the TuX-BxC-4IC cell line. Measurements have been taken at various time points up until 72 hours at various concentrations of a compound of interest, BI2536, between 1nM and 1uM. Primarily, data will be collected using qRT-PCR to gain insight into the transcriptomic changes during the potential EMT changes. Additionally, various other experiments related to migration, staining, and other essential markers will be conducted on the compound of interest and derivatives of the compound. Results: Initial results and prior work indicate that the compound of interest has moderate success in slowing cancer cell growth. Additionally, initial findings indicate that the compound may succeed in halting and potentially even reversing the EMT process. Conclusion: With this primary data set, we believe that the kinases targeted by the compound may hold potential key targets for the treatment of TNBC.Item Novel Role of Bone-Targeted Cabazitaxel Nanoparticles: Beyond the Classical Taxane Function in Metastatic Prostate Cancer Cells(2023-05) Lampe, Jana B.; Vishwanatha, Jamboor K.; Hsieh, Jer-Tsong; Gryczynski, ZygmuntBone-metastatic prostate cancer symbolizes the beginning of the end-stage disease. Bone is the primary metastatic site for prostate cancer, a condition correlated to low five-year overall survival rates, extreme pain, and poor quality of life. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. I hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuate the EMT marker, Vimentin, and lead to an increase in E-cadherin expression, which imparts epithelial characteristics to cells and inhibits cancer progression of advanced prostate cancer to distant sites. I observed the reduction of phosphorylated Src at tyrosine 416 along with increased expression of phosphorylated cofilin, cofilin at serine 3, which could affect migration and invasion pathways in cancer cells. Both increased expression of p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for prostate cancer by inhibiting invasion, migration, and EMT in prostate cancer cells. Finally, I discuss an ongoing project that also targets bone metastatic PCa with a different strategy, a liposomal drug delivery system.