Recent Progress of Nano-drug Combined with Chimeric Antigen Receptor T Cell Therapy in the Treatment of Soild Tumors / 中国肺癌杂志

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the background of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this filed.
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Cytosolic DNA-STING-NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide.

The role of NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis in acute lung injury (ALI) has been well identified previously. Stimulator of interferon genes (STING) is an indispensable adaptor protein, which could regulate inflammation and pyroptosis during infection; however, its role in lipopolysaccharide (LPS)-induced ALI remains obscure. This study aimed to explore whether STING participated in the development of LPS-induced ALI as well as the underlying mechanism. We confirmed that LPS significantly enhanced the expression and phosphorylation of STING in lung tissue and primary macrophages from mice. STING deficiency relieved inflammation and oxidative stress in LPS-treated murine lungs and macrophages. Meanwhile, STING deficiency also abolished the activation of NLRP3 inflammasome and pyroptosis; however, NLRP3 overexpression by adenovirus offset the beneficial effects of STING deficiency in macrophages treated with LPS. Additionally, the level of mitochondrial DNA (mt-DNA) significantly increased in macrophages after LPS treatment. Intriguingly, although exogenous mt-DNA stimulation did not influence the level of STING, it could still trigger the phosphorylation of STING as well as pyroptosis, inflammation, and oxidative stress of macrophages. And the adverse effects induced by mt-DNA could be offset after STING was knocked out. Furthermore, the inhibition of the sensory receptor of cytosolic DNA (cyclic GMP-AMP synthase, cGAS) also blocked the activation of STING and NLRP3 inflammasome, meanwhile, it alleviated ALI without affecting the expression of STING after LPS challenge. Furthermore, cGAS inhibition also blocked the production of cGAMP induced by LPS, indicating that mt-DNA and cGAS could activate STING-NLRP3-mediated pyroptosis independent of the expression of STING. Finally, we found that LPS upregulated the expression of transcription factor c-Myc, which subsequently enhanced the activity of STING promoter and promoted its expression without affecting its phosphorylation. Collectively, our study disclosed that LPS could activate STING in a cytosolic DNA-dependent manner and upregulate the expression of STING in a c-Myc-dependent manner, which cooperatively contribute to ALI.

Expression and clinical significance of serum ferritin in patients with lung cancer / 临床外科杂志

Objective To investigate the expression and clinical significance of serum ferritin in patients with lung cancer. Methods The relationship between preoperative serum ferritin level and corre-sponding clinicopathological data in 174 patients with lung cancer and 85 patients with benign pulmonary diseases was reviewed and analyzed. Results The level of serum ferritin in patients with lung cancer was significantly higher than that in patients with benign pulmonary diseases. For non-small cell lung cancer, patients with large-sized,poorly differentiated squamous carcinoma in advanced stage had higher serum ferritin levels than those with small-sized,highly or moderately differentiated adenocarcinoma in early stage. Conclusion Serum ferritin may play a promoting role in the development and malignant progres-sion of lung cancer.

The expression and clinical significance of miR-200b in lung cancer / 中国医师进修杂志

Objective To investigate the expression of miR-200b in lung cancer and its relationship with clinicopathological features of lung cancer.Methods The specimens of lung tumor tissue and adjacent normal lung tissue of 36 cases of lung cancer who received surgical treatment in our department were collected,and then quantitative real time PCR (qRT-PCR) was applied to determine the expression of miR-200b in lung cancer tissue and adjacent normal lung tissue.Results The expression of miR-200b in lung cancer was significantly lower than adjacent normal lung tissue (P =0.000),and in small cell lung cancer was also significantly lower than adenocarcinoma and squamous cell carcinoma (0.13 ± 0.09 vs.0.64 ± 0.33,0.75 ± 0.30) (P =0.005 and P =0.001).The expression of miR-200b in patients with positive lymph nodes,advanced stage of lung cancer and in smokers were significantly lower than those with negative lymph nodes,early stage of lung cancer and in non-smokers,respectively (0.52 ± 0.29 vs.0.87 ± 0.35,0.46 ±0.25 vs.0.90 ±0.32,0.52 ±0.27 vs.0.90 ±0.39) (P =0.004,P =0.000 and P =0.015).Conclusions Low expression of miR-200b may participate in the occurrence and progression of lung cancer,especially in small cell lung cancer,and correlates with the metastasis of lung cancer.The down-regulated expression of miR-200b may be induced by smoking.Thus,miR-200b perhaps is a new target for the treatment of lung cancer.