Objective:To investigate the clinicopathological factors predictive of lymph node metastasis (LNM) in undifferentiat-ed early gastric cancer (EGC) and to expand the possibility of endoscopic therapy for treating undifferentiated EGC.Methods:The re-searchers collected the data of 90 undifferentiated EGC patients who had undergone surgery at the Xingtai People's Hospital, Xingtai, China. The relationship between LNM and clinicopathological factors was retrospectively analyzed using univariate and multivariate lo-gistic regression analyses. Results:Univariate analysis showed that tumor size, lymphatic vessel involvement (LVI), and cancer inva-sion depth were the significant and independent risk factors for LNM. The LNM rate was 57.1%in patients with the three clinicopatho-logical risk factors. LNM was not found in patients without the three risk factors. Conclusion:Tumor size, LVI, and invasion depth are independently associated with the presence of LNM in undifferentiated EGC. Endoscopic therapy can be used to treat the patients with-out risk factors.

OBJECTIVE: Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (¹H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored. METHODS: Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by ¹H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR. RESULTS: Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS. CONCLUSION For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

BACKGROUNDStudies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs (miRNAs). We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.

METHODSMiR-503 expression was measured by quantitative real-time PCR. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA. A dual-luciferase activity assay was used to verify target genes of miR-503. Immunohistochemistry, Western blotting analysis, and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.

RESULTSMiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines. Additionally, downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line. An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503. Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins, inhibited proliferation, and sensitized the cells to DDP-induced apoptosis.

CONCLUSIONOur findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Humans ; Immunohistochemistry ; MicroRNAs ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Real-Time Polymerase Chain Reaction ; Stomach Neoplasms ; genetics

Objective: To establish a metabonomics research technique based on the combination of