Efficacy and safety of perioperative therapy for locally resectable gastric cancer:A network meta-analysis of randomized clinical trials

BACKGROUND Gastric cancer(GC)is the fifth most commonly diagnosed malignancy worldwide,with over 1 million new cases per year,and the third leading cause of cancer-related death.AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC.METHODS A comprehensive literature search was conducted,focusing on phase II/III randomized controlled trials(RCTs)assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC.The R0 resection rate,overall survival(OS),disease-free survival(DFS),and incidence of grade 3 or higher nonsurgical severe adverse events(SAEs)associated with various perioperative regimens were analyzed.A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy.RESULTS Thirty RCTs involving 8346 patients were included in this study.Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone,and the former had the highest probability of being the most effective option in this context.Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS.Owing to limited data,no definitive ranking could be determined for DFS.Considering nonsurgical SAEs,FLO has emerged as the safest treatment regimen.CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC.Further studies are required to validate these findings.

Network pharmacology-based elucidation of molecular biological mechanisms of Kanglaite injection for treatment of non-small cell lung cancer

Objective: To investigate the effective compounds, potential targets and molecular mechanism of Kanglaite injection (KLTi) in the treatment of Non-Small Cell Lung Cancer (NSCLC) based on network pharmacology. Methods: The active compounds and targets of KLTi which extracted and isolated from Coix Seed were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The related genes of NSCLC were obtained by searching the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The candidate targets of KLTi in the treatment of NSCLC were obtained after extracting the intersection network. The "drug-component-target-disease" network was constructed with the help of Cytoscape 3.7.2. The Protein- Protein Interaction networks were constructed on the STRING platform and core network modules were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of candidate genes were performed using Metascape platform, and a "pathway-target- compounds" network was constructed to further screen key genes and active compounds. Results: A total of 11 compounds, 22 candidate targets, 206 GO functions and 12 KEGG pathways were obtained. Conclusion: The active compounds of KLTi in the treatment of NSCLC are stigmasterol, stigmasterol α1 and ergosterol. The key targets are PGR, NCOA2, PTGS2, NR3C2, and PTGS1. The core GO functions included receptor activity and binding, neuronal signal transmission and hormone stimulation;KEGG mainly involves cancer pathways, neuroactive ligand-receptor interactions and calcium signaling pathways. This study reveals the molecular biological mechanism of KLTi in the treatment of NSCLC, which is speculated to be related to neuroendocrine, providing a new basis and therapeutic direction for subsequent clinical application and experimental research.

Network pharmacology-based elucidation of molecular biological mechanisms of Qizhu Yuling Decoction for treatment of esophagus cancer

Objective:To investigate the active compounds,key targets and molecular mechanism of Qizhu Yuling Decoction in the treatment of esophageal carcinoma based on network pharmacology.Methods:The active compounds of Qizhu Yuling Decoction with anti-esophageal cancer activity were screened by TCMSP and literature search,and the drug targets were searched by DrugBank and predicted by SwissTargetPrediction.The esophageal cancer-related genes were obtained from GeneCards,OMIM,DrugBank,TTD,DisGeNET,and the intersection network was selected to obtain candidate genes.The"herb-compound-target-disease"network was constructed with Cytoscape,the PPI network was constructed in STRING and core network modules were screened.Gene ontology and KEGG enrichment analysis was performed by using Metascape,and the"pathway-gene"network was constructed to further screen key targets.Results:A total of 47 active compounds(19 Astragalus,4 Zedoary turmeric,11 Atractylodes macrocephala,9 Curcuma longa,5 Clematis root,and 5 Salvia chinensis),297 candidate genes,2413 GO and 119 KEGG pathways were obtained.Conclusion:The active compounds of Qizhu Yuling Decoction in the treatment of esophageal cancer are quercetin,kaempferol,glycine and ursolic acid.The potential targets are AKT1,MAPK1,MAPK3,PIK3R1 and RELA.GO involves oxidative stress,cell cycle,apoptosis and cell death,and KEGG involves typical cancer pathways,MAPK,NF-κB and PI3K-Akt signaling pathways.This study reveals the molecular biological mechanism of Qizhu Yuling Decoction in the treatment of esophageal cancer,and speculates that the function of potential targets focuses on the interaction of multiple signaling pathways,which can antagonize the proliferation,invasion,metastasis and recurrence of esophageal cancer and improve the prognosis of patients.This study provides new evidence for subsequent new drug development,clinical application and experimental study.

Exploring the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer based on network pharmacology

Objective:To explore the molecular biological mechanism of Shugan Jianpi Decoction in treating depression-related breast cancer based on network pharmacology.Methods:The active compounds of Shugan Jianpi Decoction were explored to obtain their drug targets,and the venny network,"TCM-component-target"network,PPI network,"pathway-gene"network,GO and KEGG enrichment results were constructed using relevant softwares.Results:A total of 121 active ingredients,250 genes,2357 GO functions and 184 KEGG pathways were obtained.Conclusion:The active ingredients of Shugan Jianpi Decoction are quercetinll、kaempferol、luteolin、naringenin.The key targets are MAPK1,MAPK3,RELA,and AKT1.GO functions include cellular response to hormone stimulus、cellular response to lipid、cellular response to oxidative stress and so on.KEGG mainly involves PI3K-Akt,microRNAs,and FoxO signaling pathways.This study preliminarily explores the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer,and speculates that it mainly acts by arresting the cell cycle,inhibiting cancer cell proliferation,mediating cancer cell apoptosis,and preventing its recurrence and metastasis,which provides new evidence and new direction for subsequent clinical application and experimental research.