The organic arsenical-derived thioredoxin and glutathione system inhibitor ACZ2 induces apoptosis and autophagy in gastric cancer via ROS-dependent ER stress.

Developing novel drugs for gastric cancer (GC) is greatly needed, and a reactive oxygen species (ROS)-modulating strategy has been demonstrated to be useful for cancer treatment. However, no organic arsenical-derived ROS-modulating drug has been developed in GC. Here, we constructed ACZ2 and investigated its efficacy and potential mechanism for GC in vitro and in vivo. Our data showed that ACZ2 could inhibit GC proliferation and cause G2/M phase arrest. Moreover, ACZ2 induced ROS accumulation by depleting glutathione (GSH) and TrxR1, triggering a subsequent ER stress response by activating the PERK/EIF2/ATF4/CHOP signalling pathways, which is a crucial step for ACZ2-mediated apoptosis and autophagy. Vitally, ROS scavenger (NAC) and ER stress inhibitor (4PBA) reversed ACZ2/ROS/ER stress-mediated apoptosis and autophagy. Our in vivo results clearly demonstrated that ACZ2 suppressed tumour growth in a GC xenograft model. Collectively, our data indicated that ACZ2 is a potential agent against GC.

Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galß1-3/ß1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC.

Prognostic Value of C-Reactive Protein in Patients With Coronavirus 2019.

BACKGROUND: An elevated serum C-reactive protein (CRP) level was observed in most patients with coronavirus disease 2019 (COVID-19). METHODS: Data for COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, were retrospectively collected and analyzed from 30 January 2020 to 20 February 2020. The prognostic value of admission CRP was evaluated in patients with COVID-19. RESULTS: Of 298 patients enrolled, 84 died and 214 recovered. Most nonsurvivors were male, older, or with chronic diseases. Compared with survivors, nonsurvivors showed significantly elevated white blood cell and neutrophil counts, neutrophil to lymphocyte ratio (NLR), systemic immune inflammation index (defined by platelet count multiplied by NLR), CRP, procalcitonin, and D-dimer and showed decreased red blood cell, lymphocyte, and platelet counts. Age, neutrophil count, platelet count, and CRP were identified as independent predictors of adverse outcome. The area under the receiver operating characteristic (ROC) curve (AUC) of CRP (0.896) was significantly higher than that of age (0.833), neutrophil count (0.820), and platelet count (0.678) in outcome prediction (all P < .05). With a cutoff value of 41.4, CRP exhibited sensitivity of 90.5%, specificity of 77.6%, positive predictive value of 61.3%, and negative predictive value of 95.4%. CRP was also an independent discriminator of severe/critical illness on admission with an AUC (0.783) comparable to age (0.828) and neutrophil count (0.729) (both P > .05). CONCLUSIONS: In patients with COVID-19, admission CRP correlated with disease severity and tended to be a good predictor of adverse outcome.

MicroRNA-21-5p promotes proliferation of gastric cancer cells through targeting SMAD7.

BACKGROUND: MicroRNAs could target multiple genes by regulating the translation or degradation of mRNAs, and are involved in functions such as signal transduction pathways affecting the physiological functions of normal or tumor cells. METHODS: In this study, the expressions of miRNA-21-5p in gastric cancer tissues and SGC-7901 cells were analyzed, and the effects of miRNA-21-5p on cell proliferation, migration, invasion, and apoptosis and the expressions of target proteins SMADs in SGC-7901 cells were evaluated. Inflammatory factors interleukin 1ß and tumor necrosis factor α in siRNA-transfected SGC-7901 cells were determined by enzyme-linked immunosorbent assay. RESULTS: MiRNA-21-5p was consistently upregulated in gastric cancer tissues and SGC-7901 cells compared to normal tissues or cells. The knockdown of miRNA-21-5p with antisense oligonucleotides suppressed cell proliferation, migration, and invasion as well as inflammatory response, and promoted cell apoptosis and SMAD7 expression. CONCLUSION: These results indicate SMAD7 may mediate the oncogenic properties of miRNA-21-5p in gastric cancer, and miRNA-21-5p would be a promising strategy for the treatment of gastric cancer.

Prognostic value of circulating tumor cells detected with the CellSearch System in patients with gastric cancer: evidence from a meta-analysis.

BACKGROUND: Circulating tumor cells (CTCs) have been proposed as a marker for predicting the prognosis of cancer. However, the prognostic value of CTCs detected with the CellSearch System in patients with gastric cancer (GC) remains controversial. We performed a meta-analysis of available studies to investigate this topic. METHODS: Two authors systematically searched the studies independently in PubMed, Science Citation Index, Cochrane Database, Embase, and the references in relevant studies (up to September 2017) using keywords. Our meta-analysis was performed in Stata software, version 12.0 (2011; Stata Corp, College Station, TX, USA), with the risk ratio (RR), hazard ratio (HR), and 95% CI as the effect measures. Subgroup analyses and meta-regression were also conducted. RESULTS: Seven studies (including eight sets of data) containing 579 patients with GC from four countries were included in this meta-analysis. The pooled results showed CTC-positive status detected by the CellSearch System was significantly associated with poor overall survival (HR =2.09, 95% CI [1.71, 2.55], P<0.001, I2=31.5%) and progression-free survival (HR =2.11, 95% CI [1.25, 3.57], P=0.005, I2=75.6%) of patients with GC, regardless of sampling time. The disease control rate of CTC-positive group was lower than that of CTC-negative group for both baseline and intra-therapy, although no statistical difference existed at both sampling time points (baseline: 69.5% versus 81.8%, RR=0.79, 95% CI [0.54, 1.16], P=0.23, I2=68.0%; intra-therapy: 50.0% versus 85.9%, RR=0.24, 95% CI [0.02, 3.13], P=0.28, I2=87.4%). CONCLUSION: Our meta-analysis demonstrated that CTCs detected with the CellSearch System from the peripheral blood had significant prognostic value and might predict poor response to chemotherapy for patients with GC.