TOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway.

T-LAK-originated protein kinase (TOPK), a dual specificity serine/threonine kinase, is up-regulated and related to poor prognosis in many types of cancers. Y-box binding protein 1 (YB1) is a DNA/RNA binding protein and serves important roles in multiple cellular processes. Here, we reported that TOPK and YB1 were both highly expressed in esophageal cancer (EC) and correlated with poor prognosis. TOPK knockout effectively suppressed EC cell proliferation and these effects were reversible by rescuing YB1 expression. Notably, TOPK phosphorylated YB1 at Thr 89 (T89) and Ser 209 (S209) amino acid residues, then the phosphorylated YB1 bound with the promoter of the eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) to activate its transcription. Consequently, the AKT/mTOR signal pathway was activated by up-regulated eEF1A1 protein. Importantly, TOPK inhibitor HI-TOPK-032 suppressed the EC cell proliferation and tumor growth by TOPK/YB1/eEF1A1 signal pathway in vitro and in vivo. Taken together, our study reveals that TOPK and YB1 are essential for the growth of EC, and TOPK inhibitors may be applied to retard cell proliferation in EC. This study highlights the promising therapeutic potential of TOPK as a target for treatment of EC.

Dasabuvir suppresses esophageal squamous cell carcinoma growth in vitro and in vivo through targeting ROCK1.

Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients' survival. Through screening FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppressed ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using patient-derived xenograft tumor models. In terms of mechanism, we unveil that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating the phosphorylation of ERK1/2 by ROCK1 and the expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway.

Applications and Achievements of Single-Cell Sequencing in Gastrointestinal Cancer.

Gastrointestinal cancer represents a public health concern that seriously endangers human health. The emerging single-cell sequencing (SCS) technologies are different from the large-scale sequencing technologies which provide inaccurate data. SCS is a powerful tool for deciphering the single-cell resolutions of cellular and molecular landscapes, revealing the features of single-cell genomes, transcriptomes, and epigenomes. Recently, SCS has been applied in the field of gastrointestinal cancer research for clarifying the origin and heterogeneity of gastrointestinal cancer, acquiring micro-environmental information, and improving diagnostic and treatment methods. This review outlines the applications of SCS in gastrointestinal cancer research and summarizes the most recent advances in the field.

Relationship between polycythemia and in-hospital mortality in chronic obstructive pulmonary disease patients with low-risk pulmonary embolism.

BACKGROUNDS: Pulmonary embolism (PE) is frequent in subjects with chronic obstructive pulmonary disease (COPD) and associated with high mortality. This multi-center retrospective study was performed to investigate if secondary polycythemia is associated with in-hospital mortality in COPD patients with low-risk PE. METHODS: We identified COPD patients with proven PE between October, 2005 and October, 2015. Patients in risk classes III-V on the basis of the PESI score were excluded. We extracted demographic, clinical and laboratory information at the time of admission from medical records. All subjects were followed until hospital discharge to identify all-cause mortality. RESULTS: We enrolled 629 consecutive patients with COPD and PE at low risk: 132 of them (21.0%) with and 497 (79.0%) without secondary polycythemia. Compared with those without polycythemia, the polycythemia group had significantly lower forced expiratory volume in one second (FEV1) level (0.9±0.3 vs. 1.4±0.5, P=0.000), lower PaO2 and SpO2 as well as higher PaCO2 (P=0.03, P=0.03 and P=0.000, respectively). COPD patients with polycythemia had a higher proportion of arrhythmia in electrocardiogram (ECG) (49.5% vs. 35.7%, P=0.02), a longer hospital duration time (15.3±10.1 vs. 9.7±9.1, P=0.001), a higher mechanical ventilation rate (noninvasive and invasive, 51.7% vs. 30.3%, P=0.04 and 31.0% vs. 7.9%, P=0.04, respectively), and a higher in-hospital mortality (12.1% vs. 6.6%, P=0.04). Multivariate logistic regression analysis revealed that polycythemia was associated with mortality in COPD patients with low-risk PE (adjusted OR 1.11; 95% CI, 1.04-1.66). CONCLUSIONS: Polycythemia is an independent risk factor for all-cause in-hospital mortality in COPD patients with PE at low risk.