Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

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An operationally simple and highly selective Au/Ag bimetallic-catalyzed cross-dehydrogenative biaryl coupling between pyrazoles and fluoroarenes has been developed. With this reaction, a wide range of biheteroaryl products can be obtained in moderate to good yields with excellent functional group compatibility. The exact role of silver salts, previously overlooked in most gold-catalyzed transformations, has been carefully investigated in this biaryl coupling. Insightful experimental and theoretical studies indicate that silver acetate is the actual catalyst for C–H activation of electron-poor arenes, rather than the previously reported gold­(I)-catalyzed process. An unprecedented Au/Ag dual catalysis is proposed, in which silver­(I) is responsible for the activation of electron-poor fluoroarenes via a concerted metalation–deprotonation pathway, and gold­(III) is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that ArFnAu­(III)-mediated C–H activation of pyrazoles is most likely the rate-limiting step.

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is frequently over-expressed and serves as a prognostic marker in human cancers. However, little is known about the role of MALAT1 in gastric cancer. Here, we reported that the tissue and plasma MALAT1 levels were significantly higher in gastric cancer patients with distant metastasis (P<0.01) than patients without distant metastasis and the healthy controls. In addition, high levels of plasma MALAT1 independently correlated to a poor prognosis for gastric cancer patients (hazard ratio, 0.242; 95% CI, 0.154-0.836; P=0.036; Cox regression analysis). Functional studies revealed that knockdown of MALAT1 could inhibit cell proliferation, cell cycle progression, migration and invasion, and promote apoptosis in gastric cancer cells. Furthermore, the miR-122-IGF-1R signaling correlated with the dysregulated MALAT1 expression in gastric cancer. These data suggest that MALAT1 could function as an oncogene in gastric cancer, and high MALAT1 level could serve as a potential biomarker for the distant metastasis of gastric cancer.

Abstract. The aim of the present study was to ascertain whether plasma levels of specific microRNAs (miRNAs) are associated with distant metastasis (DM) in gastric cancer (GC). miRNA profiling was performed on 12 pairs of samples of gastric cancer with distant metastasis (GC/DM) and gastric cancer with no distant metastasis (GC/NDM); 14 differentially expressed miRNAs were identified for further inspection. Validation of these 14 miRNAs using quantitative reverse transcription PCR (qRT-PCR) on an independent validation set identified 2 differentially expressed miRNAs (miR-122 and miR-192). Further validation of these two candidate miRNAs was conducted in a disease control set, a self-paired plasma set and finally in gastric cell lines in vitro. The results revealed that when compared with GC/NDM and healthy controls (HCs), plasma levels of miR-122 were significantly lower and plasma levels of miR-192 were significantly higher in GC/DM samples (both P<0.01). The plasma miR-122 level was again lower and the plasma miR-192-level was again higher in patients with GC/DM than in patients with benign gastric ulcer (BGC) and chronic gastritis (CG) (P<0.01). Compared to the level in patients with pre-distant metastases, miR-122 was significantly decreased while miR-192 was markedly elevated in patients with post-distant metastases (P<0.01). In CTC105 and CTC141 cells, miR-122 levels were moderately lower and miR-192 levels were markedly higher when compared to the levels in the GES-1 cells. ROC analyses showed that the AUC for plasma miR-122 was 0.808 (95% CI, 0.712-0.905; P<0.01), and the AUC for plasma miR-192 was 0.732 (95% CI, 0.623-0.841; P<0.01) for distinguishing GC/ DM from GC/NDM. High expression of miR-122 in plasma independently contributed to a more favorable prognosis for GC (hazard ratio, 0.262; 95% CI, 0.164-0.816; P= 0.038; Cox regression analysis), whereas the miR-192 level was not associated with the overall survival time. Our results demonstrated that assessment of decreased circulating miR-122 and elevated circulating miR-192 levels has the potential to improve early detection of DM in GC. Higher plasma levels of miR-122 in GC may indicate a favorable prognosis.