Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials.

Objective: To systematically evaluate the safety and efficacy of docetaxel plus S-1-based therapy in gastric cancer treatment. Methods: PubMed, Embase, The Cochrane Library, and Web of Science electronic databases were searched for randomized controlled trials on docetaxel plus S-1-based therapy in the treatment of gastric cancer from the establishment of the database to 1 September 2022. Relevant studies were included per pre-defined eligibility criteria, and two researchers independently screened and assessed the included literature using Review Manager v5. Outcome measures and statistics related with efficacy and safety profiles were extracted from the included studies, and Stata v15.1 was used for pooled analysis. Results: Objective response rate (odds ratio = 2.34, 95% CI = [1.32, 4.13], p = 0.003), relapse-free survival (HR = 0.68, 95% CI = [0.58, 0.79], p < 0.001), progression-free survival (HR = 0.81, 95% CI = [0.68, 0.96], p = 0.016), and overall survival (HR = 0.86, 95% CI = [0.79, 0.95], p = 0.002) of docetaxel plus S-1-based therapy (DS-based therapy) in gastric cancer treatment were better than those of the non-DS-based therapy. However, DS-based therapy was associated with increased risk of certain adverse drug effects, such as alopecia, leukopenia, and oral mucositis. Further studies are warranted to validate the efficacy superiority of DS-based versus non-DS-based regimens as per our trial sequential analysis findings. Conclusion: DS-based therapy significantly improves patients' clinical outcomes in gastric cancer, albeit at the cost of increased toxicity. Further RCTs are needed to confirm the efficacy superiority of DS-based regimens.

The transcription factor Ikaros inhibits cell proliferation by downregulating ANXA4 expression in hepatocellular carcinoma.

The occurrence and progression of hepatocellular carcinoma (HCC) are affected by complicated signal transduction factors. Our previous study identified Ikaros as a novel reactivated therapeutic target that acts as a transcriptional repressor and reactivates anticancer mechanisms in HCC therapy. Annexin A4 (ANXA4) is a member of the Annexin family that plays an essential role in several cancers, but it has not been investigated in HCC proliferation. Using cDNA microarrays, ANXA4 was shown to be associated with Ikaros in Ikaros-overexpressing cells. The aim of this work was to characterize the relationship between Ikaros and ANXA4 and the role of ANXA4 in HCC. The effect of Ikaros on ANXA4 was analyzed in HCC cell lines and HCC patient samples, and functional recovery experiments were performed between Ikaros and ANXA4. Furthermore, the effect of ANXA4 on cell proliferation in vitro was analyzed by MTT and colony formation assays in HCC cells. We used a subcutaneous xenograft model to elucidate the role of ANXA4 in vivo. We found that ANXA4 overexpression promotes HCC cell proliferation, but Ikaros can inhibit ANXA4 expression by repressing its promoter activity. Moreover, we demonstrated that downregulated expression of ANXA4 inhibited HCC cell proliferation and tumorigenesis in vitro and in vivo. Our findings indicate that ANXA4 may be a critical factor in HCC tumorigenesis. Ikaros is an attractive inhibitor of ANXA4 and may function as an anticancer agent in HCC.

Id4 promotes cell proliferation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in the world, especially in China. As a member of the inhibitor of differentiation (Id) family, Id4 has been reported to function in many cancer types, but relatively little is known about its role in HCC. The purpose of this study was to investigate the potential relationship between Id4 and HCC development and the underlying mechanism involving the function of Id4 in HCC. METHODS: We used quantitative real-time polymerase chain reaction and Western blotting to examine the RNA and protein expression of Id4. In addition, we used Cell Counting Kit-8 assay and colony formation assay to identify the function of Id4 in the regulation of cell proliferation in human HCC. RESULTS: We found that the expression of Id4 protein was up-regulated in tumor tissues from HCC patients. Overexpression of Id4 promoted HCC cell proliferation, clonogenicity in vitro, and tumorigenicity in vivo. Id4 knockdown experiments showed that silencing Id4 blocked the proliferation and colony formation ability of HCC cells in vitro. Furthermore, overexpression of CCAAT/enhancer-binding protein ß inhibited Id4 expression in HCC cells. CONCLUSION: Id4 may be developed as a potent therapeutic agent for the treatment of HCC, but more details about the underlying mechanisms of action are needed.

Inhibitory effects of transcription factor Ikaros on the expression of liver cancer stem cell marker CD133 in hepatocellular carcinoma.

CD133 is a cellular surface glycoprotein that has been reported as a marker for the enrichment of cancer stem cells (CSCs). However, the regulatory mechanism of CD133 remains unknown. CSCs have been proposed to contribute to radioresistance and multi-drug resistance. The elucidation of key regulators of CD133 and CSCs is critical for the development of CSC-targeted therapy. In this study, we showed that Ikarosinhibited the expression of CD133 via direct binding to the CD133 P1 promoter and repressed the tumorigenic and self-renewal capacity of CD133(+) cancer stem-like cells in hepatocellular carcinoma (HCC). We found that Ikaros interacted with CtBP as a transcription repressor complex, which inhibited CD133 expression in HCC. We also demonstrated that Ikaros expression was up-regulated by ETS1 which activity was regulated by MAPKs pathway. Furthermore, decreased expression of Ikaroswas significantly associated with poor survival in HCC patients. Overall, our study identifies that Ikaros plays a role as a transcription repressor in HCC and is a new reactivated therapeutic target for the treatment of HCC. Meanwhile, our findings provide evidence that Ikaros could be an attractive inhibitor of the target gene CD133, which reactivates anticancer mechanisms in targeted CSC therapy.