MicroRNA-630 Suppresses Epithelial-to-Mesenchymal Transition by Regulating FoxM1 in Gastric Cancer Cells.

In the present study, we investigated the functional role of microRNA (miR)-630 in epithelial-to-mesenchymal transition (EMT) of gastric cancer (GC) cells, as well as the regulatory mechanism. Cells of human GC cell line SGC 7901 were transfected with miR-630 mimic or miR-630 inhibitor. The transfection efficiency was confirmed by qRT-PCR. Cell migration and invasion were determined by Transwell assay. Protein expression of E-cadherin, vimentin, and Forkhead box protein M1 (FoxM1) was tested by Western blot. Moreover, the expression of FoxM1 was elevated or suppressed, and then the effects of miR-630 abnormal expression on EMT and properties of migration and invasion were examined again, as well as protein expression of Ras/phosphoinositide 3-kinase (PI3K)/AKT related factors. The results showed that (i) the EMT and properties of migration and invasion were statistically decreased by overexpression of miR-630 compared to the control group but markedly increased by suppression of miR-630. However, (ii) abnormal expression of FoxM1 reversed these effects in GC cells. Moreover, (iii) expression of GTP-Rac1, p-PI3K, and p-AKT was decreased by miR-630 overexpression but increased by FoxM1 overexpression. (iv) The decreased levels of GTP-Rac1, p-PI3K, and p-AKT induced by miR-630 overexpression were dramatically elevated by simultaneous overexpression of FoxM1. In conclusion, our results suggest that miR-630 might be a tumor suppressor in GC cells. MiR-630 suppresses EMT by regulating FoxM1 in GC cells, supposedly via inactivation of the Ras/PI3K/AKT pathway.

ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway.

A disintegrin and metalloproteinase-17 (ADAM17) is a member of the metalloproteinase superfamily and involved in the cleavage of ectodomain of many transmembrane proteins. ADAM17 is overexpressed in a variety of human tumors, which is associated with tumor development and progression. In the present study, we sought to investigate the expression and function of ADAM17 in hypoxia-treated hepatocellular carcinoma (HCC) cells. Western blot analysis was used to measure the expression of ADAM17 in HCC cell lines (Hep3B and HepG2 cells). Annexin V/PI double staining was performed to analyze the effects of ADAM17 on hypoxia-mediated cisplatin resistance. ADAM17 expression was upregulated by hypoxia treatment in HCC cells at both mRNA and protein levels. Overexpression of ADAM17 reduced cisplatin-induced apoptosis in HCC cells, accompanies by less cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Forced expression of ADAM17 enhanced the phosphorylation of epidermal growth factor receptor (EGFR) and Akt without affecting the expression of total EGFR and Akt. Pretreatment with EGFR inhibitor AG1478 or phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 rescued ADAM17-mediated cisplatin resistance of HCC cells. ADAM17 silencing attenuated hypoxia-induced cisplatin resistance and enhanced the accumulation of cleaved caspase-3 and PARP. Western blot analysis showed that overexpression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor, upregulated the expression of ADAM17 and HIF-1α silencing downregulated the expression of ADAM17 in hypoxia-treated HCC cells, indicating the regulation of ADAM17 by HIF-1α. Taken together, our results indicated that ADAM17 is upregulated by hypoxia and contributes to hypoxia-induced cisplatin resistance via EGFR/PI3K/Akt pathway.

Model Checking Temporal Logic Formulas Using Sticker Automata.

As an important complex problem, the temporal logic model checking problem is still far from being fully resolved under the circumstance of DNA computing, especially Computation Tree Logic (CTL), Interval Temporal Logic (ITL), and Projection Temporal Logic (PTL), because there is still a lack of approaches for DNA model checking. To address this challenge, a model checking method is proposed for checking the basic formulas in the above three temporal logic types with DNA molecules. First, one-type single-stranded DNA molecules are employed to encode the Finite State Automaton (FSA) model of the given basic formula so that a sticker automaton is obtained. On the other hand, other single-stranded DNA molecules are employed to encode the given system model so that the input strings of the sticker automaton are obtained. Next, a series of biochemical reactions are conducted between the above two types of single-stranded DNA molecules. It can then be decided whether the system satisfies the formula or not. As a result, we have developed a DNA-based approach for checking all the basic formulas of CTL, ITL, and PTL. The simulated results demonstrate the effectiveness of the new method.

Efficacy and advantages of modified Traditional Chinese Medicine treatments based on "kidney reinforcing" for chronic aplastic anemia: a randomized controlled clinical trial.

OBJECTIVE: To compare the efficacy of modified treatments based on "kidney reinforcing" in the management of chronic aplastic anemia (CAA), and explore their advantages and specialties. METHODS: One hundred and eleven patients with CAA were randomly divided into three groups: kidney reinforcing alone (KA), "kidney reinforcing and Qi tonifying" (KQ), and "kidney reinforcing and blood circulation invigorating" (KC). Normal and positive control groups were also formed. All patients were treated for 6 months (two courses). Hemograms, Traditional Chinese Medicine (TCM) syndrome scores, and therapeutic effects were assessed, and changes in T-lymphocyte subsets, regulatory T cells and cytokines were detected. RESULTS: The KQ and KC groups had lower TCM syndrome scores than the positive control group after 6 months (P < 0.05). The KQ group had a higher overall efficacy than the positive control group after 3 months (P < 0.05), while platelet counts increased in the KC group after 6 months (P < 0.05). CD3+ T-lymphocyte ratios decreased only in the KQ group, while CD3 + CD4 + CD8 − Tlymphocytes increased only in the KC group after 6 months (P < 0.05). Levels of interferon-γ, tumor necrosis factor tor-α, interleukin (IL)-2 and IL-6 decreased and levels of IL-4 and IL-10 increased in all treated groups after 6 months. Levels of IL-6 in the KQ and KC groups were lower than those in the positive control group (P < 0.05). CONCLUSION: Treatments based on kidney reinforcing have a rebalancing effect on cytotoxic and T helper cells, and regulate expression of interferon- γ, IL-2, IL-6 and IL-4. KQ may be more effective in treating CAA, and KC may have an advantage in platelet recovery.

[The application of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in diagnosing dysplasia and chronic atrophic gastric-carditis in population with high risk of gastric-cardia adenocarcinoma].

OBJECTIVES: To evaluate the serum biomarkers for diagnosis of gastric cardia dysplasia (DYS) and chronic atrophic gastric-carditis (CAG) and to provide a novel screening method for high risk population of gastric-cardia adenocarcinoma (GCA). METHODS: Proteomic spectra were generated by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS) and weak cation exchange protein chip system. A set of spectra derived from analysis of serum from 143 symptom-free subjects at high-risk area for GCA, including 63 cases with histologically normal gastric cardia epithelia, 57 of CAG and 23 of DYS, were analyzed by bioinformatics like decision tree classification algorithm. The sensitivity and the specificity for test group were performed by using 10-fold cross validation classification with the decision tree classification model. RESULTS: One protein spot with a ratio of mass to charge (M/Z) of M3894. 0 was selected to build a decision tree classification model to identify the case with DYS or normal. With this classification model, the sensitive rate for DYS identification was 87% (20/23). Two proteins with M/Z of M2942. 15 and M33316. 6 were used to build a decision tree classification model. With this model, the sensitivity for discriminating CAG from normal was 93% (53/57) and the specificity was 92 (58/63). CONCLUSIONS: The gastric cardia lesions of DYS and CAG could be identified by SELDI-TOF-MS technique specifically in symptom-free subjects at high incidence area for GCA. The present findings provide a new screening way for high-risk subjects with CGA.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

[Serum proteomic profiles of the subjects with esophageal precancerous and cancerous lesions from Linzhou, an area with high incidence of esophageal cancer in Henan Province, Northern China].

BACKGROUND & OBJECTIVE: Some molecular changes occurred in esophageal precancerous and cancerous lesions could be reflected in the serum, but the clinical application is limited because of their low sensitivity and specificity. Serum proteomic profiling is much desirable in identifying the proteins closely related to esophageal carcinogenesis. This study was to characterize the serum protein profiles of the subjects with normal esophagus, esophageal precancerous and cancerous lesions from Linzhou, the area with the highest incidence of esophageal carcinoma (EC) in Henan Province, Northern China. METHODS: Proteomic spectra were generated with surface-enhanced laser desorption/inionation-time of flight-mass spectra (SELDI-TOF-MS) and weak cation exchange (WCX2) protein chip system, and analyzed by bioinformatics like decision tree classification algorithm on a set of serum from 130 symptom-free subjects [including 63 cases with normal esophageal epithelia, 40 with basal cell hyperplasia (BCH), and 27 with dysplasia (DYS)] and 30 EC patients from Linzhou. RESULTS: One protein in BCH group with a ratio of mass to charge (M/Z) of M9 306.61 u, 1 in DYS group with a M/Z ratio of M13 765.9 u, and 2 in EC group with M/Z ratios of M2 942.15 u and M15 953.4 u were selected to build 3 decision tree classification models to identify the subjects with BCH, DYS, and EC, respectively. With these classification models, the sensitivities of identifying BCH, DYS and EC were 57.5% (23/40), 88.8% (24/27) and 96.6% (29/30), respectively, in the training sets, and 57.5% (23/40), 66.6% (18/27) and 60.0% (18/30), respectively, in the test sets; the specificities of identifying BCH, DYS and EC were 96.8% (61/63), 63.4% (40/63) and 92.0% (58/63), respectively, in the training sets, and 95.2% (60/63), 71.4% (45/63) and 84.1% (53/63), respectively, in the test sets. CONCLUSION: The protein sets with M/Z ratios of M9 306.61 u, M13 765.9 u, M2 942.15 u, and M15 953.4 u may contain promising serum biomarkers for screening the subjects with high-risk of EC.