Survivin as a potential biomarker in the diagnosis of bladder cancer: A systematic review and meta-analysis.

Early detection, diagnosis, and treatment take on critical significance in preventing and treating bladder cancer. As indicated by numerous studies, survivin can serve as a biomarker of bladder cancer, whereas the results of a wide variety of studies have been controversial. This paper is to assess the accuracy of survivin in the diagnosis of bladder cancer by a meta-analysis. The studies regarding the diagnosis of bladder cancer using survivin were systematically retrieved from the CNKI, WanFang, CBM, VIP, Web of science, cochrane library and pubmed were extracted, and the literature quality was assessed. Meta-analysis was conducted using STATA 16.0 MP. 2,082 relevant studies were searched, and 40 studies were finally covered for meta-analysis. The pooled specificity and pooled sensitivity of survivin mRNA was 0.95 (95%CI: 0.91, 0.97) and 0.94 (95%CI: 0.88, 0.97). The pooled specificity and pooled sensitivity of survivin protein reached 0.95 (95%CI: 0.90, 0.97) and 0.87 (95%CI: 0.78, 0.92). The pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the curve, and diagnostic odds ratio for survivin mRNA reached 17.7 (95%CI: 10.3, 30.6), 0.07 (95%CI: 0.04, 0.12), 0.98 (95%CI: 0.97, 0.99) and 266 (95%CI: 114, 621), respectively. For survivin protein was 16.4 (95%CI: 7.9, 33.9), 0.14 (95%CI: 0.08, 0.24), 0.97 (95%CI: 0.95, 0.98) and 117 (95%CI: 38, 357), respectively. Survivin takes on great significance in diagnosing bladder cancer. However, due to some limitations in the number and quality of covered studies, this conclusion should be validated through additional higher quality clinical studies.

Robustness of Cyber-Physical Supply Networks in Cascading Failures.

A cyber-physical supply network is composed of an undirected cyber supply network and a directed physical supply network. Such interdependence among firms increases efficiency but creates more vulnerabilities. The adverse effects of any failure can be amplified and propagated throughout the network. This paper aimed at investigating the robustness of the cyber-physical supply network against cascading failures. Considering that the cascading failure is triggered by overloading in the cyber supply network and is provoked by underload in the physical supply network, a realistic cascading model for cyber-physical supply networks is proposed. We conducted a numerical simulation under cyber node and physical node failure with varying parameters. The simulation results demonstrated that there are critical thresholds for both firm's capacities, which can determine whether capacity expansion is helpful; there is also a cascade window for network load distribution, which can determine the cascading failures occurrence and scale. Our work may be beneficial for developing cascade control and defense strategies in cyber-physical supply networks.

[Anti-proliferation and chemo-sensitization effects of apigenin on human lung cancer cells].

OBJECTIVE: To investigate the antitumor effect of apigenin on human lung cancer cells. METHODS: The anti-proliferation and sensitization effects of apigenin on human lung cancer cells was accessed by counting cells after Trypan blue staining and MTS assay. RESULTS: (1) Apigenin significantly suppressed the proliferation of four types of human lung cancer cells (A549:P=0.041, H460:P=0.050, LTEP-a2:P=0.039, H292:P=0.016); (2) Apigenin significantly increased the susceptibility of human lung cancer cells to antitumor drugs (P<0.05 or P<0.01) in a synergistic way (almost all of the combination index values are less than 1). CONCLUSION: Apigenin widely inhibits cell proliferation of various lung cancer cell lines in a dose-dependent manner and the combination treatment of apigenin and antitumor drugs is very effective in human lung cancer cells, and Nrf2-ARE pathway may contribute to the mechanism.

Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor regulating the expression of a battery of cytoprotective genes. Constitutive Nrf2 activation in many tumors enhances cell survival and resistance to anticancer drugs. Using a cell-based ARE-reporter assay we discovered that the flavonoid luteolin is a potent Nrf2 inhibitor. Luteolin inhibited ARE-driven gene expression redox-independently. In non-small-cell lung cancer A549 cells, which possess constitutively active Nrf2, luteolin elicited a dramatic reduction in Nrf2 at both the mRNA and the protein levels, leading to decreased Nrf2 binding to AREs, down-regulation of ARE-driven genes, and depletion of reduced glutathione. After transcription was blocked with actinomycin D, 1µM luteolin decreased the Nrf2 mRNA level by 34% in 30 min, indicating its role in accelerating Nrf2 mRNA turnover. At physiological concentrations, luteolin significantly sensitized A549 cells to the anticancer drugs oxaliplatin, bleomycin, and doxorubicin. However, knockdown of Nrf2 using siRNA essentially abolished the induced sensitivity by the flavonoid, implying the importance of inhibiting Nrf2 for its activity. Our study demonstrates that an Nrf2 inhibitor can enhance the responsiveness of cancer cells to chemotherapeutic drugs and indicates the potential application of luteolin as a natural sensitizer in chemotherapy.