To compare the efficacy and safety of different Claudin (CLDN)18.2-directed regimens in advanced gastric/gastroesophageal junction adenocarcinoma. PubMed, Web of Science, CNKI, and Wanfang databases were searched up to June 2026. Single-arm trials evaluating CLDN18.2-targeted gastric/gastroesophageal junction adenocarcinoma therapies were included. Meta-analysis was performed to pool objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and safety outcomes. Ten studies (710 patients) were included. The pooled mPFS was 4.19 months (95
Qishen Yiqi Dripping Pills (QSYQ) have shown promising therapeutic effects on cardiovascular diseases. Recent studies have reported their potential in mitigating doxorubicin-induced cardiotoxicity (DIC), but the primary active ingredients and specific mechanisms remain unclear. A total of 2740 differentially expressed genes (DEGs) were screened out. GSEA results were mainly enriched in Glycolysis, Apoptosis, Cellular Senescence, PI3K/Akt Signaling Pathway, TGF Beta Signaling Pathway, etc. Weighted gene co-expression network analysis yielded 1520 key module genes, and 1134 DIC-related genes were obtained by intersecting with DEGs. A total of 130 active ingredients and 943 target genes of QSYQ were obtained, and 50 common targets were identified after intersecting with DIC-related genes. The top 5 active ingredients were DFV, quercetin, Vestitone, formononetin and (6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano[3,2-c]chromen-3-ol. GO and KEGG enrichment analyses showed a close relationship with the HIF-1 signaling pathway and its upstream and downstream components. Three key genes identified were EP300, JUN, and CREBBP. Receiver operating characteristic analysis demonstrated good diagnostic value for these key genes, and their DOX-induced expression alterations were reversed by QSYQ (limited experimental evidence). Notably, the experimental validation of JUN showed a trend opposite to that observed in the bioinformatics analysis. Molecular docking revealed good binding capabilities of the primary active ingredients with the key genes. QSYQ may alleviate DIC through EP300, JUN, and CREBBP, providing new evidence for the use of QSYQ in ameliorating DIC.
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting factor and determinant of treatment continuation in patients receiving anticancer drugs. CIPN often persists even after treatment discontinuation and negatively impacts patients’ quality of life. At present, the risk factors for CIPN development remain unclear. This study aimed to exploratively examine the association between genetic polymorphisms and CIPN in Japanese patients with metastatic pancreatic cancer treated with gemcitabine and nab-paclitaxel (GnP) as first-line chemotherapy. This exploratory analysis of the GENESECT dataset included 65 patients with metastatic pancreatic cancer who received GnP therapy. The association of 14 genetic polymorphisms with CIPN was analyzed by multivariate Firth logistic regression with Benjamini–Hochberg correction for multiple comparisons. The Kaplan–Meier curves among genetic polymorphisms were analyzed using log-rank test to compare the cumulative dosage of nab-paclitaxel until CIPN ≥ grade 2. Results were considered significant at p < 0.05. The AA and AC variants of LGALS3 rs4652 tended to be associated with CIPN ≥ grade 2 (adjusted odds ratio (OR), 0.248; 95
Cemiplimab is a fully human PD-1 inhibitor approved for cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer. Post-market safety surveillance is essential given the broad and evolving indications for immune checkpoint inhibitors. All FAERS reports with cemiplimab as the primary suspect drug were extracted. Proportional Reporting Ratios (PRR), Reporting Odds Ratios (ROR), and chi-squared statistics were calculated for each adverse event. Disproportionality signals were defined by PRR >= 2, chi-squared >= 3.841, and a minimum of 15 reports. A total of 1,460 cemiplimab reports were identified in the FAERS database. Twenty-two adverse events met all signal detection criteria. The strongest signals were observed for myocarditis (PRR 54.35, n = 40), myositis (PRR 46.10, n = 25), pemphigoid (PRR 36.06, n = 16), and pneumonitis (PRR 19.37, n = 31). Immune-mediated adverse events predominated, consistent with the mechanism of PD-1 blockade. FAERS disproportionality analysis identifies a signal profile for cemiplimab dominated by immune-related adverse events across cardiac, pulmonary, dermatologic, and endocrine systems. These findings are consistent with the known immunotoxicity of PD-1 inhibitors and support heightened clinical vigilance for myocarditis and immune-mediated pneumonitis.
Kinase inhibitors are commonly used in research and clinical practice. Among them, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as afatinib and osimertinib, constitute an important subclass. The aim of this study was to create an irreversible covalent EGFR TKI exhibiting endogenous fluorescence, i.e., intrinsic fluorescence without the need for additional fluorochromes. These compounds, designated SQI-2, SLT40, and SLT41, were successfully developed and shown to effectively inhibit the EGFR, EGFRL858R/T790M, and EGFRvIII kinases. The developed compounds are suitable for a range of cytochemical analyses, including real-time assays. The proposed TKIs may serve as research and diagnostic tools and represent precursors of new types of therapeutic compounds.
