Applying Untargeted Lipidomics to Evaluate the Efficacy of Combined Neoadjuvant Chemotherapy and Immunotherapy for Esophageal Squamous Carcinoma Treatment.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant tumor with a poor prognosis due to insidious symptoms that make early diagnosis difficult. Despite the combination of multiple treatment modalities, the recurrence and mortality rates of ESCC remain high. Neoadjuvant chemotherapy combined with immunotherapy is an emerging treatment modality that improves the prognosis of patients with ESCC. However, owing to the presence of hyperprogression and pseudoprogression, the currently used methods cannot accurately evaluate the efficacy of this therapy in patients, thus creating an evaluation bias and depriving these patients of the opportunity to benefit. We used untargeted lipidomics to identify the differences in lipid composition between cancer specimens and normal tissue specimens in the neoadjuvant chemotherapy combined with the immunotherapy group and the surgery-alone group of esophageal cancer patients and constructed a prediction model based on sphingomyelin 12:1;2O/30:0 and triglyceride (TG) 60:3 | TG 18:0_24:1_18 using a machine learning approach, which helps to better evaluate the neoadjuvant efficacy of combination therapy and better guide the treatment of ESCC.

Atractylenolide III ameliorated reflux esophagitis via PI3K/AKT/NF-κB/iNOS pathway in rats.

Reflux esophagitis (RE), an esophageal inflammation caused by reflux of gastric contents, often damages the lower esophagus, seriously affecting the quality of life of patients. This study aims to investigate the therapeutic effects and underlying molecular mechanisms of atractylenolide III (ATL III) on RE model rats. In this research, the RE rat model is established sequentially following hemipyloric ligation, cardia transection, and hydrochloric acid perfusion. Further, the RE-induced rats are intragastrically administrated with ATL III (0.6, 1.2, and 2.4 mg/kg/D) for 28 days to evaluate ATL III therapeutic effects. To study the molecular mechanism, RE rats are treated with a phosphoinositide-3 kinase (PI3K) agonist (740 Y-P) combined with ATL III. The histopathological changes in the esophagus are eventually observed by hematoxylin & eosin (H&E) staining. In addition to changes in gastric pH and levels of reactive oxygen species (ROS), enzyme-linked immunosorbent assay (ELISA) and Western blot analyses are used to detect the expression levels of tumor necrosis factor-α (TNF-α, mmol/L), interleukin (IL)-8, IL-6, IL-1ß in the esophageal tissues. As a result, the lesions in the esophageal tissues of RE rats are alleviated, decreasing the macroscopic observation scores of the esophageal mucosa after ATL III treatment,. The experimental results indicated significantly increased pH value of the gastric contents and reduced ROS, thiobarbituric acid reactants (TBARS), TNF-α, IL-8, IL-6, and IL-1ß levels, as well as expression levels of p-PI3K, p-AKT, iNOS, and nuclear NF-κB proteins in esophageal tissues. In conclusion, the study indicated that ATL III could efficiently treat RE in rats by inhibiting oxidative stress and inflammatory damage through the PI3K/AKT/NF-κB/iNOS pathway.

Circ_ZNF778_006 promoted ESCC progression by upregulating HIF-1α expression via sponging miR-18b-5p.

In multiple malignant tumors, circular RNAs (circRNAs) are believed to play a crucial role. Our prior results demonstrated that circ_ZNF778_006 was significantly increased in esophageal squamous cell carcinoma (ESCC) tissues, but the roles of circ_ZNF778_006 in ESCC is still not clear. The expression of circ_ZNF778_006 was compared in different pathological grades of ESCC. And the expression levels of circ_ZNF778_006, miR-18b-5p, HIF-1α were analyzed by qRT-PCR and Western blot, respectively. Plasmid transfection techniques were applied to prepare ESCC cells with silenced or overexpressed genes (CircZNF778_006, miR-18b-5p). The CCK8 kit was used to determine cell proliferation, and the Transwell assay was used to measure the migration and invasion. The effects of circ_ZNF778_006 on tumor growth was investigated in vivo. Furthermore, luciferase reporter gene assay and RNA-binding protein immunoprecipitation (RIP) were performed to verify the targeting relationship between miR-18b-5p and circZNF778_006, miR-18b-5p and HIF-1α. The expression of circ_ZNF778_006 was positively correlated with pathological grade in ESCC. Circ_ZNF778_006 significantly inhibited sensitivity to 5-fluorouracil & cisplatin. It could promote the proliferation, invasion, migration in ESCC cells and accelerated tumor growth in vivo. Furthermore, circ_ZNF778_006 could upregulate the expression of HIF-1α via sponing miR-18b-5p. Circ_ZNF778_006 promoted ESCC progression by upregulating HIF-1α expression via sponging miR-18b-5p.

lncRNA-LET Regulates Glycolysis and Glutamine Decomposition of Esophageal Squamous Cell Carcinoma Through miR-93-5p/miR-106b-5p/SOCS4.

Background: Dysregulated non-coding RNAs exhibit critical functions in various cancers. Nonetheless, the levels and corresponding functions of cirCSNX14 in esophageal squamous cell carcinoma (ESCC) yet remain to be elucidated. Methods: Initially, the aberrant low levels of lncRNA-LET within ESCC tissues are validated via qRT-PCR observations. Moreover, the effects of lncRNA-LET upregulation on cell proliferation in vitro are determined. In addition, a series of assays determining the mechanistic views related to metabolism is conducted. Furthermore, the effects of lncRNA-LET in affecting tumor growth are investigated in vivo in a mouse model. Moreover, the interactions between lncRNA-LET and its networks are predicted and determined by RNA immunoprecipitation-assisted qRT-PCR as well as luciferase reporter assays. Results: The downregulation of lncRNA-LET is correlated to the poor prognosis of ESCC patients. Moreover, the upregulated expression of lncRNA-LET could have reduced the cell viability. In vivo tumor inhibition efficacy assays showed that an increase of lncRNA-LET presented excellent inhibitory effects on cancer proliferation as reflected by tumor weight and volume in mice. Finally, the mechanistic views regarding the effects of miR-106b-5p or miR-93-5p and SOCS4 on ESCC are related to the feedback of lncRNA-LET. Conclusion: Collectively, this study suggested that lncRNA-LET miR-93-5p or the miR-106b-5p-SOCS4 axis may provide great potential in establishing ESCC therapy.