Idelalisib, a PI3K inhibitor, specifically targeting p110δ, has been approved for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. However, the mechanisms of action of idelalisib in colon cancer cells are not well understood. We investigated how idelalisib suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. In this study, we found that idelalisib treatment induces PUMA in colon cancer cells irrespective of p53 status through the p65 pathway following AKT inhibition and glycogen synthase kinase 3β (GSK3β) activation. PUMA is necessary for idelalisib-induced apoptosis in colon cancer cells. Idelalisib also synergized with 5-FU or regorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and antitumor effect of idelalisib in xenograft model. These results demonstrate a critical role of PUMA in mediating the anticancer effects of idelalisib in colon cancer cells and suggest that PUMA induction can be used as an indicator of idelalisib sensitivity, and also have important implications for it clinical applications.
Objective: Diagnosing gastric cancer (GC) at early stages is important for reducing its mortality. This study evaluated the diagnostic value of serum pepsinogen (PG) I, PGII, and gastrin-17 (G17) levels in screening for early-stage GC. Methods: Serum levels of PGI, PGII, and G17 were measured in patients with upper digestive tract symptoms or GC family histories, and the PGI to PGII ratio (PGR) was calculated. Receiver operator characteristic curves were used to determine the thresholds of PGI, PGR, and G17 for GC diagnosis. Results: Among the 949 patients examined by gastroscopy, 13 (1.37%) had GC, including five cases of early-stage GC and eight cases of progressive GC. PGI, PGR, and G17 showed good specificity and sensitivity for early-stage and progressive GC. The optimal thresholds of PGI, G17, and PGR were 71.85 lg/L, 15.65 pmol/L and 5.04 for the diagnosis of early-stage GC, respectively, and were 42.55 lg/L, 20.55 pmol/L, and 2.79 for the diagnosis of progressive GC, respectively. Conclusion: Combining PG and G17 serum levels with gastroscopy could be a promising approach to screen for early-stage GC.
Background: Approximately half of people with heart failure have chronic kidney disease (CKD). Tolvaptan is reported to be effective in treating heart failure. However, the safety and efficacy of its use in patients with CKD is uncertain. In this study, we conducted a protocol for systematic review and meta-analysis to investigate the efficacy and safety of tolvaptan on patients with heart failure and CKD. Methods: This study protocol has been registered in the PROSPERO and the registration number is CRD42022368148. The consent of this protocol report is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement guidelines. We will include randomized controlled trials related to tolvaptan in patients with heart failure and CKD. Two research members will electronically and independently search 4 English databases (EMBASE, PubMed, National Guideline Clearinghouse, and Cochrane Central Register of Controlled Trials) and 4 Chinese databases (Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP Database) from their inception to November 2022. The risk of bias in each included study will be assessed utilizing the Cochrane Collaboration’s risk of bias tool. All statistical analyses will be conducted using the software program Review Manager version 5.3. Results: The results of this systematic review will be published in a peer-reviewed journal. Conclusion: This review can provide convincing evidence to help clinicians make decisions when dealing with heart failure and CKD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.