RÉSUMÉ
In a randomized controlled trial with time-to-event endpoint, some commonly used statistical tests to test for various aspects of survival differences, such as survival probability at a fixed time point, survival function up to a specific time point, and restricted mean survival time, may not be directly applicable when external data are leveraged to augment an arm (or both arms) of an RCT. In this paper, we propose a propensity score-integrated approach to extend such tests when external data are leveraged. Simulation studies are conducted to evaluate the operating characteristics of three propensity score-integrated statistical tests, and an illustrative example is given to demonstrate how these proposed procedures can be implemented.
RÉSUMÉ
BACKGROUND: The Danggui-Kushen herb pair (DKHP) is a classic prescription that has long been used in combination with chemotherapeutic drugs to improve the immune status of patients with breast cancer (BC), however, the active components and the underlying pharmacological mechanisms remain unclear. Therefore, this study aimed to elucidate the possible mechanism of action of DKHP against BC-based comprehensive strategy combining network pharmacology, molecular docking, and cellular experiments. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to obtain the relevant compounds in DKHP. Genecards and the National Center for Biotechnology Information databases were used to predict BC targets. Then, drug-compound- target, andprotein-protein interaction networks were constructed to forecast the promising protein targets of DKHP and identify the primary interactions that occur between the protein targets and compounds. Finally, the predicted candidate targets were validated using docking techniques and in vitro experiments. RESULTS: A total of 30 potential active compounds and 173 intersecting pharmacological targets were identified in DKHP. Gene Ontology enrichment analysis revealed that the inflammatory response, positive regulation of protein phosphorylation, and cellular response to lipopolysaccharide were closely related to DKHP treatment in BC. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the PI3K/AKT pathway may be crucial for DKHP intervention in BC. Therefore, key targets could be AKT1, TP53, VEGR, CASP3, TNF, and IL6. Molecular docking analysis suggested that hyperforin, kushenin, and kushenol T had good binding ability to Akt, p53, and Caspase 3. The in vitro experiment showed that the DKHP extract promoted the apoptosis of MCF-7 cells via the PI3K/Akt signaling pathway. These results corresponded to the predictions produced using the network pharmacology approach. CONCLUSION: Hyperforin, kushenin, kushenol T, and other active compounds in DKHP can regulate multiple signaling pathways and targets, such as AKT1, TP53, and CASP3, thereby playing preventive and therapeutic roles in BC.