FIGURE SUMMARY
Title

An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity

Authors
Wakai, E., Suzumura, Y., Ikemura, K., Mizuno, T., Watanabe, M., Takeuchi, K., Nishimura, Y.
Source
Full text @ Pharmaceuticals (Basel)

Venn diagrams of genes contained in the gene expression signature associated with cisplatin-induced nephrotoxicity (GES-CIN). Venn diagrams of unique and shared differentially expressed genes in untreated vs. cisplatin-treated mouse kidneys (GSE106993 and GSE130814) or human kidney organoids (GSE145085). Differentially expressed genes were identified using a false discovery rate threshold of 1% (Table S1). (A,B) show genes upregulated and downregulated by cisplatin treatment, respectively.

Enrichment of CIN-associated differentially expressed genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The 208 genes in the GES-CIN (Table S2) were analyzed with ClueGO using KEGG as the reference database to identify significantly enriched functional networks.

Maximum values of serum creatinine (Scr) and blood urea nitrogen (BUN) in patients treated for 14 days with cisplatin and either ramosetron or palonosetron. Patients with head and neck cancer (n = 103) received cisplatin and 5-fluorouracil together with ramosetron (n = 26) or palonosetron (n = 77). p values determined by the Mann–Whitney U test.

Kaplan–Meier overall survival analysis of patients treated with cisplatin and either ramosetron or palonosetron. Patients with head and neck cancer (n = 103) received cisplatin and 5-fluorouracil, together with either ramosetron (n = 26) or palonosetron (n = 77), to treat chemotherapy-induced nausea and vomiting. p value determined using the log-rank test.

Effects of 5-hydroxytryptamine receptor 3 (5-HT3R) antagonists on the survival of zebrafish exposed to cisplatin. Zebrafish (5 days post-fertilization) were treated with the indicated combinations of drugs for 24 h, and survival was assessed. Mean ± SEM of n = 6. ** p < 0.01 vs. no drug group, ## p < 0.01 vs. cisplatin only group by Dunnett’s test.

Acknowledgments
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