Background: Spread through air spaces (STAS) is a spreading phenomenon of lung cancers, which is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. To date, several articles have reviewed the studies concerning the significance of STAS; however, most articles focused on the prognosis without summarizing the significance of STAS on other aspects. In this review, we comprehensively summarized the current literature related to STAS, so as to explore the clinical significance of STAS from multiple perspectives. Main Body: This section provided a comprehensive overview of the significance of STAS from multiple perspectives and summarized current controversies and challenges in the diagnosis and clinical application. Conclusion: STAS is a conspicuous spreading phenomenon of lung cancers indicating worse prognosis; nevertheless, the treatment strategy for patients with STAS remains to be discussed. Further studies are needed to elaborate whether a STAS-positive patient who underwent limited resection needs a second operation or postoperative adjuvant treatment. Meanwhile, the internal mechanism of STAS formation is largely undiscovered. Whether the capability of detachment-migration-reattachment in STAS tumor cells is achieved at the time of primary tumorigenesis or in the progress of tumor development needs to be studied, and the related signal pathways or genetic alterations need to be explored. With this information, it may be possible to improve the prognosis of patients with STAS-positive lung cancers.

Background: This study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system. Methods: In total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically. Results: STAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis. Conclusions: Our findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.

Fluctuations of conserved quantities are sensitive observables to probe the signature of QCD phase transition and critical point in heavy-ion collisions. With the UrQMD model, we have studied the centrality and energy dependence of various order cumulants and cumulant ratios (up to fourth order) of net-proton,net-charge and net-kaon multiplicity distributions in Au+Au collisions at √ sNN = 7. 7, 11.5, 19.6, 27, 39, 62.4, 200 GeV. The model results show that the production mechanism of the particles and anti-particles have significant impacts on the cumulants of netparticles multiplicity distributions and show strong energy dependence. We also made comparisons between model calculations and experimental data measured in the first phase of the beam energy scan (BES) program by the STAR experiment at RHIC. The comparisons indicate that the baryon conservation effect strongly suppress the cumulants of net-proton distributions at low energies and the non-monotonic energy dependence for the net-proton κσ 2 at the most central Au+Au collisions measured by the STAR experiment can not be described by the UrQMD model. Since there has no physics of QCD phase transition and QCD critical point implemented in the UrQMD, the model results provide us baselines and qualitative estimates about the non-critical background contributions to the fluctuations observables in heavy-ion collisions.

Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. However, the cellular targets and anticancer mechanism of PSN-A in various cancers including prostate cancer remain largely unexplored. In the present study, we have shown that PSN-A inhibits proliferation and induces apoptosis in prostate cancer cells in a dose-dependent manner. Further mechanistic study have shown that anticancer activity of PSN-A in prostate cancer cells is associated with ROS generation, Bcl-2 family proteins modulation, mitochondrial membrane potential disruption and ultimately activation of caspase-3 and cleavage of PARP. Moreover, we found that PSN-A inhibits JAK2/STAT3 signaling and augments doxorubicin toxicity in prostate cancer cells. Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer.

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