Arterial Spin Labeling and Amide Proton Transfer Imaging can Differentiate Glioblastoma from Brain Metastasis: A Systematic Review and Meta-Analysis.

BACKGROUND: Currently, arterial spin labeling (ASL) and amide proton transfer (APT) imaging have shown potential for distinguishing glioblastoma from brain metastases. Thus, a meta-analysis was conducted to investigate this further. METHODS: An extensive and comprehensive search was conducted in 6 English and Chinese databases according to predefined inclusion and exclusion criteria, encompassing data up to July 2023. Data from eligible literature were extracted, and bivariate models were employed to calculate pooled sensitivities, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve. RESULTS: The meta-analysis included 11 articles. For ASL, the pooled sensitivity was 0.77 (95% confidence interval [CI], 0.63-0.87), and the pooled specificity was 0.87 (95% CI, 0.77-0.93). The pooled PLR was 5.89 (95% CI, 2.97-11.69), the pooled NLR was 0.26 (95% CI, 0.15-0.47), the pooled DOR was 22.33 (95% CI, 6.89-72.34), and AUC was 0.90 (95% CI, 0.87-0.92). For APT imaging, the pooled sensitivity was 0.78 (95% CI, 0.70-0.85), and the pooled specificity was 0.86 (95% CI, 0.77-0.92). The pooled PLR was 5.51 (95% CI, 3.24-9.37), the pooled NLR was 0.25 (95% CI, 0.17-0.37), the pooled DOR was 21.99 (95% CI, 10.28-47.03), and the AUC was 0.90 (95% CI, 0.87-0.92). CONCLUSIONS: This meta-analysis suggest that both ASL and APT imaging exhibit high accuracy in distinguishing between glioblastoma and brain metastasis.

Niclosamide Revitalizes Sorafenib through Insulin-like Growth Factor 1 Receptor (IGF-1R)/Stemness and Metabolic Changes in Hepatocellular Carcinoma.

Sorafenib is the first approved systemic targeting agent for advanced HCC; however, when used alone, drug resistance can result in considerably reduced efficacy. Here, we demonstrate that niclosamide, an antihelminthic agent approved by the US Food and Drug Administration, can be repurposed to increase sorafenib sensitivity in sorafenib-resistant HCC cells. We generated sorafenib-resistant HCC cell lines (HepG2215_R and Hep3B_R) with elevated IGF-1R levels and strong properties in terms of stemness and epithelial-mesenchymal transition. Niclosamide was found to increase sorafenib sensitivity effectively in both cell lines and their organoids. The underlying mechanism involves the modulation of cancer stemness, IGF-1R/p-IGF1R/OCT4, and metabolic changes. The combination of sorafenib and niclosamide, but not linsitinib, effectively suppressed the IGF-1R/OCT4 expressions, yielded a synergistic combination index (CI), and attenuated stemness-related properties such as secondary tumor sphere formation and cell migration in sorafenib-resistant HCC cells. Notably, niclosamide significantly suppressed the sorafenib-induced IGF-1R phosphorylation prompted by IGF-1 treatment. Niclosamide effectively downregulated the sorafenib-induced gene expression associated with glycolysis (GLUT1, HK2, LDHA, and PEPCK), stemness (OCT4), and drug resistance (ABCG2) and enhanced the ability of sorafenib to reduce the mitochondrial membrane potential in vitro. The synergistic effect of a combination of niclosamide and sorafenib in vivo was further demonstrated by the decreased tumor size and tumor volume resulting from apoptosis regulation. Our results suggest that niclosamide can enhance sorafenib sensitivity in sorafenib-resistant HCC cells through IGF-1R/stemness regulation and metabolic changes. Our findings highlight a practical clinical strategy for enhancing sorafenib sensitivity in HCC.