Platinum-based anticancer anticancer drugs drugs represented represented by by cisplatin cisplatin play play important important roles roles in in the the treatment of of various various solid solid t Show more
Platinum-based anticancer anticancer drugs drugs represented represented by by cisplatin cisplatin play play important important roles roles in in the the treatment of of various various solid solid tumors. tumors. However, However, their their applications applications are are largely largely compromised compromised by by drug drug treatment resistanceand andside side effects. effects. Much Much effort effort has has been been made made to to circumvent circumvent the the drug drug resistance resistanceand Show less
The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but
these tumors quickly develop resistance to this treatment. We have observed
increased phosphorylation of AKT1/mTOR/4EBP1 a Show more
The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but
these tumors quickly develop resistance to this treatment. We have observed
increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in
FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that
stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/
mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence
that NSC49L- and TRAIL-mediated sensitization is synergistically induced in
p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21
binds with procaspase 3 and prevents the activation of caspase 3. We have shown
that TRAIL induces apoptosis through the activation of caspase 3 by NSC49Lmediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These
studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and
how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells. Show less
Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in Show more
Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related Show less
Background: Drug-drug interactions (DDIs) are a significant source of morbidity and adverse drug events (ADEs), particularly in situations of polypharmacy and complex medication regimens. While rules- Show more
Background: Drug-drug interactions (DDIs) are a significant source of morbidity and adverse drug events (ADEs), particularly in situations of polypharmacy and complex medication regimens. While rules-based software integrated in electronic health records (EHRs) has demonstrated proficiency in identifying DDIs present in medication regimens, large language model (LLM) based identification requires thorough benchmarking and performance evaluation using high-quality datasets for safe use. The purpose of this study was to develop a series of Show less