Boyao Yu

BACKGROUND: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. MAIN BODY: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. CONCLUSION: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.

Background. Sepsis, which could cause a systemic inflammatory response, is a life-threatening disease with a high morbidity and mortality rate. There is evidence that brain injury may be related to severe systemic infection induced by sepsis. The brain injury caused by sepsis could increase the risk of mortality in septic patients, which seriously affects the septic patient’s prognosis of survival. Although there remains a focus on sepsis research, clinical measures to prevent and treat brain injury in sepsis are not yet available, and the high mortality rate is still a big health burden. Therefore, it is necessary to investigate the new molecules or regulated pathways that can effectively inhibit the progress of sepsis. Objective. NLR family pyrin domain-containing 3 (NLRP3) increased in the procession of sepsis and functioned as the key regulator of pyroptosis. Heat shock factor 1 (HSF1) can protect organs from multiorgan dysfunction syndrome induced by lipopolysaccharides in mice, and NLRP3 could be inhibited by HSF1 in many organs. However, whether HSF1 regulated NLRP3 in sepsis-induced brain injury, as well as the detailed mechanism of HSF1 in brain injury, remains unknown in the sepsis model. In this research, we try to explore the relationship between HSF1 and NLRP3 in a sepsis model and try to reveal the mechanism of HSF1 inhibiting the process of brain injury. Methods. In this study, we used wild-type mice and hsf1-/- mice for in vivo research and PC12 cells for in vitro research. Real-time PCR and Western blot were used to analyze the expression of HSF1, NLRP3, cytokines, and pyrolytic proteins. EthD-III staining was chosen to detect the pyroptosis of the hippocampus and PC12 cells. Results. The results showed that HSF1 is negatively related to pyroptosis. The pyroptosis in cells of brain tissue was significantly increased in the hsf1-/- mouse model compared to hsf1+/+ mice. In PC12 cells, hsf1 siRNA can upregulate pyroptosis while HSF1-transfected plasmid could inhibit the pyroptosis. HSF1 could negatively regulate the NLRP3 pathway in PC12 cells, while hsf1 siRNA enhanced the pyroptosis in PC12 cells, which could be reversed by nlrp3 siRNA. Conclusion. These results imply that HSF1 could alleviate sepsis-induced brain injury by inhibiting pyroptosis through the NLRP3-dependent pathway in brain tissue and PC12 cells, suggesting HSF1 as a potential molecular target for treating brain injury in sepsis clinical studies.

BACKGROUND: Exosomes are defined as small membranous vesicles. After RNA content was discovered in exosomes, they emerged as a novel approach for the treatment and diagnosis of cancer. Long noncoding RNAs (lncRNA), a kind of specific RNA transcript, have been reported to function as tumor growth, metastasis, invasion, and prognosis by regulating the tumor microenvironment in exosomes. This study aims at exploring the potential diagnostic of exosomal lncRNA in solid tumors. METHODS: A meta-analysis conducted from January 2000 to October 2019 identified publications in the English language. We searched all relevant English literature from the Web of Science, EMBASE, and PubMed databases through October 1, 2019. The articles were strictly screened by our criteria and critiqued using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: There were 28 studies with 19 articles (4017 patients) identified, including studies on gastric cancer, laryngeal squamous cell carcinoma, colorectal cancer, cholangiocarcinoma, breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, nonsmall cell lung cancer, and prostate cancer. A meta-analysis showed that the combined value of sensitivity in 29 studies was 0.74 (95% confidence interval [CI], 0.7-0.78), and the combined value of specificity in the studies was 0.81 (95% CI, 0.78-0.83). This suggests the high diagnostic efficacy of liquid exosomes in cancer patients. It is statistically insignificant in terms of sex, ethnicity, and year. The diagnostic power of urinary system tumors was found to be higher than that of digestive system tumors by several subgroup analyses. CONCLUSIONS: We performed a meta-analysis and literature review of 28 studies that included 4017 patients with 10 malignant cancer types. Mechanistically, our study demonstrated that lncRNAs in exosomes could be a promising bioindicator for the diagnosis and prognosis of solid tumors. INPLASY Registration Number: INPLASY202060083.