No abstract

This study aims to investigate the significance and mechanism of artesunate involved in suppressing the proliferation of gastric cancer in vitro and in vivo. In the in-vitro experiments, artesunate inhibited the growth of gastric cancer cell lines (SGC-7901, BGC-823, and AGS) with concentration-dependent activity, with no significant effect on GES-1 cells. BGC-823 cells treated with artesunate showed the typical morphologic features of oncosis rather than apoptosis. Meanwhile, we observed calcium overload, downregulation of vascular endothelial growth factor expression, and upregulation of calpain-2 expression in the artesunate-treated BGC-823 cells. In addition, the in-vivo study showed that artesunate produced a dose-dependent tumor regression in nude mice. The antitumor activity of 240 mg/kg artesunate was similar to that of 10 mg/kg docetaxel. Furthermore, compared with the control group, no significant difference was observed in the body weight of artesunate-treated nude mice other than docetaxel-treated nude mice. These observations show that artesunate has concentration-dependent inhibitory activities against gastric cancer in vitro and in vivo by promoting cell oncosis through an impact of calcium, vascular endothelial growth factor, and calpain-2 expression.

No abstract

One of the most visible tragedies by industrial water pollution is Minamata disease, methylmercury poisoning caused by eating contaminated fish, which has killed more than 100 people and paralyzed several thousand people around Minamata Bay, Japan and the adjacent Yatsushiro Sea since 1956. The cause of Minamata disease was confirmed, not by analyzing environmental samples such as sediments (containing more than 600 ppm of Hg) or fish (at least 20 ppm) at the bay, but by symptoms of Minamata disease patients that resembled previous mercury poisoning reported in a European medical journal. Mercury dispersion was traced for 22 years to collect mercury concentration measurements in Yatsushiro Sea surface sediments at 24 fixed stations. The analytical results of mercury revealed four trends of mercury movement from the bay: 1) a rapid increase in Hg concentrations up to 1984; 2) a dramatic decrease in mercury concentrations after an artificial mercury decontamination project began in 1984; 3) a strange drop in mercury contents due to an historical rainfall in the region in 1982 and; 4) natural decontamination, which has been underway since 1985. The tragedy at Minamata has provided many lessons which have shaped the scientific field in environmental research, especially in the area of water quality.

US28 expression is predictive of poor prognosis and may promote CRC.

Histone acetyltransferases and deacetylases are two groups of enzymes whose opposing activities govern the dynamic levels of reversible acetylation on specific lysine residues of histones and many other proteins. Gastrointestinal (GI) carcinogenesis is a major cause of morbidity and mortality worldwide. In addition to genetic and environmental factors, the role of epigenetic abnormalities such as aberrant histone acetylation has been recognized to be pivotal in regulating benign tumorigenesis and eventual malignant transformation. Here we provide an overview of histone acetylation, list the major groups of histone acetyltransferases and deacetylases, and cover in relatively more details the recent studies that suggest the links of these enzymes to GI carcinogenesis. As potential novel therapeutics for GI and other cancers, histone deacetylase inhibitors are also discussed.

Hitherto, it has been identified that numerous basic-helix-loop-helix (bHLH) transcription factors play vital roles in tumor initiation and progression. Atonal homolog 8 (ATOH8) is a member of the bHLH family of transcription factors, which participates in embryogenesis and the development of various tissues. Several studies have demonstrated that ATOH8 is involved in the progression of malignancies; however, the effects of ATOH8 in colorectal cancer (CRC) remain unknown. The aim of the present study was to explore the expression and function of ATOH8 in CRC. The present study included 106 paired CRCs and peritumoral samples. The expression of ATOH8 was evaluated by immunohistochemistry, and the results were compared with the clinical outcomes of the patients. Furthermore, cell proliferation, cell cycle distribution, wound healing and cytotoxicity assays were performed in colon cancer cell line SW620. Immunohistochemical analyses revealed that the expression of ATOH8 in CRC tissues was significantly increased compared with the peritumoral tissues, and that the high expression of ATOH8 was associated with a high serum carcinoembryonic antigen (CEA) level and a worse overall survival. In vitro assays revealed that ATOH8 knockdown in colon cancer cells inhibited cell proliferation, induced cell cycle arrest at the S phase, and increased the percentage of apoptotic cells and sensitivity to 5-fluorouracil (5-FU). The present study suggests that ATOH8 promotes the progression of CRC and may potentially serve as a novel prognostic predictor and potential therapeutic target in CRC.

Some studies have demonstrated that Rab11-family interacting proteins (Rab11-FIPs) are connected with the tumorigenesis, and they may act as tumor promoters in some cancers. The clinicopathological significance of Rab11-family interacting protein 4 (Rab11-FIP4) expression and its possible effects on pancreatic cancer (PC) are still undiscovered. In this study, Rab11-FIP4 protein expression level in 60 PC specimens and pair-matched non-cancerous samples were detected by immunohistochemistry analysis. The results were analysed and compared with each patients' clinical data. Rab11-FIP4 expression in PC tissues increased significantly more than that of adjacent non-cancerous tissues (P=0.0001). Overexpression of Rab11-FIP4 in the PC tissues was significantly related to tumor size (P=0.0001), histological grade (P=0.028), metastasis (P=0.001) and TNM stage (P=0.004) but not with age (P=0.832), gender (P=0.228) or tumor site (P=0.875). Kaplan-Meier survival analysis showed that overexpression of Rab11-FIP4 was significantly related to overall survival time (P=0.0036). In addition, Rab11-FIP4 in PANC-1 pancreatic cancer cells were successfully knocked-out using the CRISPR/Cas9 system. Rab11-FIP4 knockout in PANC-1 cells inhibited cell growth, invasion and metastasis, and arrested cell cycle progression, but did not alter apoptosis. Our findings suggest that overexpression of Rab11-FIP4 predicts poor clinical outcomes for pancreatic cancer and contributes to pancreatic tumor progression.