Chenxi Zhong

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world, and the development of new therapeutic targets is needed. Recent studies have shown that aerobic glycolysis, also known as the Warburg effect, mediated the anti-apoptotic effects in cancer cells. Lactate dehydrogenase A (LDHA) which executed the final step of aerobic lactate production has been reported to be involved in the tumor progression. However, the function of LDHA in ESCC has not been investigated. In this study, it was found that LDHA was up-regulated in ESCC clinical samples. Knockdown of the expression of LDHA inhibited cell growth and cell migration in vitro as well as tumorigenesis in vivo. With regard to the molecular mechanism, silencing the expression of LDHA was related to decreased AKT activation and cyclin D1 expression and increased cleavage of PARP and caspase 8. Taken together, our findings suggest that LDHA plays an important role in the progression of ESCC by modulating cell growth, and LDHA might be a potential therapeutic target in ESCC.

Background: Intrinsic or acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is common, thus strategies for the management of EGFR-TKIs resistance are urgently required. Ferroptosis is a recently discovered form of cell death that has been implicated in tumorigenesis and resistance treatment. Accumulating evidence suggests that ferroptosis can be therapeutically exploited for the treatment of solid tumors; however, whether ferroptosis can be targeted to treat EGFR mutant lung cancer and/or overcome the resistance to EGFR-TKIs is still unknown.Methods: The effect of ferroptosis inducers on a panel of EGFR mutant lung cancer cell lines, including those with EGFR-TKI intrinsic and acquired (generated by long-term exposure to the third-generation EGFR-TKI osimertinib), was determined using cytotoxicity assays. Further, drug candidates to enhance the effect of ferroptosis inducers were screened through implementing WGCNA (weighted gene co-expression network analysis) and CMAP (connectivity map) analysis. Flow cytometry-based apoptosis and lipid hydroperoxides measurement were used to evaluate the cell fates after treatment.Results: Compared with EGFR-TKI-sensitive cells, those with intrinsic or acquired resistance to EGFR-TKI display high sensitivity to ferroptosis inducers. In addition, Vorinostat, a clinically used inhibitor targeting histone deacetylase, can robustly enhance the efficacy of ferroptosis inducers, leading to a dramatic increase of hydroperoxides in EGFR mutant lung cancer cells with intrinsic or acquired resistance to EGFR-TKI. Mechanistically, Vorinostat promotes ferroptosis via xCT downregulation.Conclusions: Ferroptosis-inducing therapy shows promise in EGFR-activating mutant lung cancer cells that display intrinsic or acquired resistance to EGFR-TKI. Histone deacetylase inhibitor (HDACi) Vorinostat can further promote ferroptosis by inhibiting xCT expression.

OBJECTIVE: The psychological resilience of postoperative non-small cell lung cancer (NSCLC) patients is influenced by many factors. The purpose of this study is to investigate the current state of psychological resilience and identify its influencing factors in postoperative NSCLC patients. METHODS: This descriptive cross-sectional study used a convenience sampling method and recruited 382 inpatients from two Class A hospitals in Hunan, China. The Connor-Davidson Resilience Scale (CD-RISC), Strategies Used by People to Promote Health (SUPHH), Medical Coping Modes Questionnaire (MCMQ), and Multidimensional Scale of Perceived Social Support (MSPSS) were used. RESULTS: Postoperative NSCLC patients' psychological resilience was at a low level, with a score of (57.18 ± 8.55). Stepped Linear Regression showed that the related influencing factors of psychological resilience of postoperative NSCLC patients were age (β = -0.313, P < .001), family average income (β = 0.143, P < .001), self-efficacy (β = 0.416, P < .001), confrontation (β = 0.116, P < .001) and acceptance-resignation (β = -0.155, P < .001), which could explain 58.0% of the total variation in psychological resilience (F = 103.68, P<.001). CONCLUSIONS: Psychological resilience is positively predicted by average income, self-efficacy, confrontation, but negatively predicted by age and acceptance-resignation. Self-efficacy is the most important variable influencing psychological resilience in postoperative NSCLC patients. In the future, a series of targeted interventions need to be implemented to strengthen patients' self-efficacy and psychological resilience, which can also improve the quality of life of postoperative NSCLC patients.