Oxaliplatin-triggered chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment that limits the efficacy of chemotherapy and negatively impacts patients' quality of life dramatically. Notably, inhibition of TXNIP with verapamil reduced oxidative stress levels. Our results demonstrated the use of DRG explants as an efficient model to study the mechanisms of CIPN and screen for potential treatments.
In some cell lines, the fiber modification F5RGD10(2C) or verapamil treatment further improves actual spread efficiency. Nelfinavir inhibits spread and plaque formation of oncolytic adenoviruses with the 19KSS-iLQ125Ter modifications, irrespective of adenovirus death protein (ADP) expression...We identified an insertion site downstream of the L3-23K region that supports relatively high hPH20 activity while preserving the enhanced oncolytic potency of the virus. Combining 19KSS-iLQ125Ter with hPH20 expression may potentially improve therapeutic benefit in glioma.
P=N/A, N=60, Recruiting, The First Affiliated Hospital of Army Medical University (Southwest Hospital); The First Affiliated Hospital of Army Medical University (Southwest Hos | Not yet recruiting --> Recruiting | Initiation date: Aug 2025 --> Nov 2025
Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels, as determined by UPLC-MS/MS, and synergistically decreased cell viability as observed in CCK-8 assay. These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells, with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration. Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.
These findings highlight tetrandrine's dual profile: a promising natural antiangiogenic agent with demonstrable efficacy, yet with significant cardiotoxic and developmental liabilities. This study provides crucial mechanistic insight into both its therapeutic and toxicological actions, establishing a translational foundation for its further development.
In this study, we evaluated the ability of elacridar, a dual P-gp and BCRP inhibitor, to overcome MDR in W1, an ovarian cancer cell line sensitive to Paclitaxel (PAC) and its PAC-resistant variants. These findings highlight elacridar as a promising compound for reversing MDR in ovarian cancer and emphasize the importance of 3D models in preclinical drug evaluation. Further studies in advanced in vitro and in vivo models are required to assess the potential of elacridar better.
In metabolic stability assays using human liver microsomes, AQQ6 exhibited relatively low intrinsic clearance (Clint) and an improved half-life (T1/2) compared to verapamil. However, pharmacokinetic studies in rats indicated poor oral bioavailability (%F = 4.2), likely due to extensive hepatic metabolism in rat liver microsomes. Molecular dynamics simulations targeting MAPK8, the protein likely involved in AQQ6 activity, were conducted to elucidate molecular-level binding interactions.