Circ_0028826 Promotes Growth and Metastasis of NSCLC via Acting as a Sponge of miR-758-3p to Derepress IDH2 Expression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR-758-3p. IDH2, Bcl2, Bax, and E-cadherin protein levels were detected using a western blot. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR-758-3p and circ_0028826 or IDH2 was validated using a dual-luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model. RESULTS: Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR-758-3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR-758-3p to inhibit tumor growth in vivo. CONCLUSION: Circ_0028826 promoted the development of NSCLC via regulation of the miR-758-3p/IDH2 axis, providing a new strategy for NSCLC treatment.

Combination treatment with anti-HER2 therapeutic antibody RC48, PD-1 inhibitor, radiotherapy, and granulocyte macrophage-colony stimulating factor (GM-CSF) in patient with metastatic gastric cancer: a case report.

HER2 overexpression/amplification is a prevalent driver in various types of cancer, including gastric cancer (GC). Limited options are available for patients with HER2-positive metastatic gastric cancer, particularly those who do not respond to the standard therapy of HER2 antibody trastuzumab combined with chemotherapy. Previous research suggests that combining a PD-1 inhibitor with radiotherapy and granulocyte macrophage-colony stimulating factor (PRaG regimen) may enhance the antitumor effects in patients with chemotherapy-resistant metastatic solid tumors. In this case study, we presented a potential treatment strategy of a patient having HER2-positive and PD-L1-negative gastric adenocarcinoma. The patient showed rapid tumor progression even after surgery and multiple trastuzumab plus chemotherapy treatments. To address this, we employed a novel anti-HER2 antibody called RC48 in combination with PRaG regimen therapy (PRaG3.0). The patient demonstrated a positive response after two treatment cycles and achieved a progression-free survival time of 6.5 months. This case highlights the potential of four-combination therapies for treating refractory, multiorgan, HER2-positive, PD-L1-negative metastatic gastric cancer. Additionally, varying radiation doses in targeting dual foci is critical to enhance tumor immunotherapy.

Combining Network Pharmacology, Molecular Docking and Preliminary Experiments to Explore the Mechanism of Action of FZKA Formula on Non-small Cell Lung Cancer.

BACKGROUND: Clinically, Fuzhengkangai formulation (FZKA) has been proven to have significant therapeutic effects on non-small lung cancer (NSCLC), although the mechanism is unknown. We aimed to explore the potential mechanism of FZKA in the treatment of NSCLC in this study. METHODS: We obtained the active components and targets of FZKA by TCMSP. The target genes of NSCLC were searched from OMIM, GEO (GSE18842), and GeneCards database. Cytoscape (3.7.2) software was used to construct a "drug-compound-cross-target interaction" interaction network, and the STING database was used to analyze previous cross-target interactions. Meanwhile, the results were visualized and processed by performing GO enrichment analysis and KEGG signaling pathway enrichment analysis at the target site. The core targets were docked with active components through AutoDockTools-1.5.6 software. Finally, we used cellular experiments to validate the bioinformatics predictions. RESULTS: There were 40 active and 465 potential genes from the TCMSP database. Key active chemicals, namely Quercetin, Kaempferol, Luteolin, and Tanshinone IIA, and 176 targets were deemed as targets of FZKA against NSCLC by PPI network analysis. GO and KEGG enrichment analyses suggest that FZKA acts primarily through the PI3K-AKT and MAPK signaling pathways in the treatment of NSCLC. Moreover, cellular assays showed that Quercetin, Kaempferol, Luteolin, and Tanshinone IIA not only reduced the viability of A549 cells and promoted apoptosis but also significantly decreased the p-AKT/AKT and p-ERK1/2/ERK1/2 ratios. CONCLUSION: Our data suggested that FZKA can be involved in the treatment of NSCLC through multiple components, targets and pathways.