Synergy vanderbilt3/15/2023 A Jun N-terminal kinases (JNK) inhibitor inhibited apoptosis in treated cells and significantly reduced death receptor expression indicating JNK activation by ER stress sensitizes PCa cells to TRAIL-induced apoptosis by upregulating DR4/DR5 expression. Taxane and TRAIL combination synergistically amplified apoptosis strongly suggesting that taxanes sensitize prostate cancer cells to TRAIL. DU145 and PC3 cells displayed no significant reduction in cell viability when treated with soluble TRAIL, docetaxel, or cabazitaxel alone indicating that both cell lines are resistant to TRAIL and taxanes individually. In this study, we sensitized androgen-independent and TRAIL-resistant prostate cancer cells to TRAIL-mediated apoptosis via taxane therapy and examined the mechanism of sensitization. TNF-related apoptosis inducing ligand (TRAIL) is an anticancer agent that is selectively cytotoxic to cancer cells however, many human cancers are resistant to TRAIL. Kidambi said his next step is collaborating with the Vanderbilt University Medical Center to explore therapeutic applications.Docetaxel and cabazitaxel are guideline-chemotherapy treatments for metastatic castration-resistant prostate cancer (mCRPC), which comprises the majority of prostate cancer deaths. Department of Energy at MIT and faculty startup funding at Vanderbilt. The team included collaborators from MIT, Oxford University and Oak Ridge National Laboratory and was funded by the U.S. Kidambi’s paper on his work, Facile Fabrication of Large-Area Atomically Thin Membranes by Direct Synthesis of Graphene with Nanoscale Porosity, appeared online today in Advanced Materials. “We think these membranes could offer transformative advances for small molecule separation, fine chemical purification, buffer exchange and a number of other processes including lab-scale dialysis.” Here, we make membranes that are one atom thick and show much higher permeance – up to 100 times greater than the state-of-the-art commercial dialysis membranes – specifically in the low molecular weight cut-off range. “Diffusion across these layers is very slow. “Most commercial membranes achieve separation at small size ranges by making a dense polymer layer that is several microns thick with tortuous pores,” Kidambi said. Polymer casting on nanoporous CVD graphene for facile nanoporous atomically thin membrane fabrication. The team used these atomically thin membranes to demonstrate separation of salt and small molecules from small proteins. “Continuing on with the baking analogy, this was like dough transforming into porous bread – the support polymer layer.” The dip transformed the polymer to a porous support layer with graphene on the top, effectively forming an atomically thin membrane. The team turned to conventional polymer membrane manufacturing techniques and decided to spread a thin polymer layer on the nanoporous graphene and dipped the stack into a water bath. However, the atomically thin graphene with nanoscales holes needed to be supported to form a membrane. “It reminded me of decreasing the temperature while baking a chocolate cake to get a different texture,” Kidambi said. The team dialed down the temperature during graphene and found this resulted in nanoscale holes – missing carbon atoms from the two-dimensional layer of them bonded in a hexagonal lattice. The team initially focused on developing methods to directly form nanoscale holes into an atomically thin material. Kidambi and his team more recently applied that overlap in their own work to address some of the most critical challenges in membrane research: achieving high flow-through membranes without compromising filtration performance. They explained the landscape on how the technology evolved and advanced and how the field is ripe for collaborations. In a review published earlier this year in Advanced Materials, Assistant Professor of Chemical and Biomolecular Engineering Piran Kidambi and his team explored new interest in using materials only one atom thick for membrane applications. Where researchers who worked with two-dimensional materials and those who worked with membranes were once separate, synergistic opportunities are resulting in exciting new developments at their intersection, a Vanderbilt University chemical and biomolecular engineering professor has both opined and proven. Synergy in two-dimensional materials, membranes research clear in professor’s new work
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