MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer

Background\ud The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer.\ud \ud Methods\ud The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo.\ud \ud Results\ud MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo.\ud \ud Conclusions\ud This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer

Метод расчета зависимости динамики доходов работников от уровня образования в Республике Беларусь

We report a study of the process e(+)e(-) -&gt; (D*(D) over bar*)(0)pi(0) using e(+)e(-) collision data samples with integrated luminosities of 1092 pb(-1) at root s = 4.23 GeV and 826 pb(-1) at root s = 4.26 GeV collected with the BESIII detector at the BEPCII storage ring. We observe a new neutral structure near the (D*(D) over bar*)(0) mass threshold in the pi(0) recoil mass spectrum, which we denote as Z(c)(4025)(0). Assuming a Breit-Wigner line shape, its pole mass and pole width are determined to be (4025.5(-4.7)(+2.0) +/- 3.1) MeV/c(2) and (23.0 +/- 6.0 +/- 1.0) MeV, respectively. The Born cross sections of e(+)e(-) -&gt; Z(c)(4025)(0)pi(0) -&gt; (D*(D) over bar*)(0)pi(0) are measured to be (61.6 +/- 8.2 +/- 9.0) pb at root s = 4.23 GeV and (43.4 +/- 8.0 +/- 5.4) pb at root s = 4.26 GeV. The first uncertainties are statistical and the second are systematic.Funding: The BESIII Collaboration thanks the staff of BEPCII and the IHEP computing center for their strong support. This work is supported in part by the National Key Basic Research Program of China under Contract No. 2015CB856700; the National Natural Science Foundation of China (NSFC) under Contracts No. 11125525, No. 11235011, No. 11275266, No. 11322544, No. 11335008, and No. 11425524; the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Program; the CAS Center for Excellence in Particle Physics (CCEPP); the Collaborative Innovation Center for Particles and Interactions (CICPI); the Joint Large-Scale Scientific Facility Funds of the NSFC and the CAS under Contracts No. 11179007, No. U1232201, and No. U1332201; the CAS under Contracts No. KJCX2-YW-N29 and No. KJCX2-YW-N45; the 100 Talents Program of the CAS; INPAC and the Shanghai Key Laboratory for Particle Physics and Cosmology; German Research Foundation DFG under Contract No. Collaborative Research Center CRC-1044; the Istituto Nazionale di Fisica Nucleare, Italy; the Ministry of Development of Turkey under Contract No. DPT2006K-120470; the Russian Foundation for Basic Research under Contract No. 14-07-91152; the U.S. Department of Energy under Contracts No. DE-FG02-04ER41291, No. E-FG02-05ER41374, No. DE-FG02-94ER40823, and No. DESC0010118; the U.S. National Science Foundation; the University of Groningen (RuG) and the Helmholtzzentrum fuer Schwerionenforschung GmbH (GSI), Darmstadt; and the WCU Program of National Research Foundation of Korea under Contract No. R32-2008-000-10155-0.</p

The Effect of Electrode Thickness on the High-Current Discharge and Long-Term Cycle Performance of a Lithium-Ion Battery

Six groups of electrodes with different thickness are prepared in the current study by using Li[Ni1/3Co1/3MN1/3]O2 as the active substance; the electrode thicknesses are 71.8, 65.4, 52.6, 39.3, 32.9, and 26.2 &mu;m, respectively, with similar internal microstructures. The effect of electrode thickness on the discharge rate, pulse discharge, internal resistance, and long-term cycle life of a pouch cell are investigated. The results show that, with the decrease in the electrode thickness from 71.8 &mu;m to 26.2 &mu;m, the high-current-discharge performance of the cell gradually improves, the pulse-discharge power density under 50% SOC increases from 1561 W/Kg to 2691 W/Kg, the Rdis decreases from 8.70 m&Omega; to 3.34 m&Omega;, and the internal resistance decreases from 3.36 m&Omega; to 1.21 m&Omega;. In the long-term cycle-life test, the thinner the electrode thickness, the less the capacity fading of the cell; the internal resistance of the cell is observed with the increase in the cycle index

Metformin inhibited esophageal squamous cell carcinoma proliferation in vitro and in vivo and enhanced the anti-cancer effect of cisplatin.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied. In the present study, we found that metformin exhibited not only an anti-proliferation ability in a dose and time dependent manner but also a proapoptosis effect in a dose dependent manner in ESCC cell line KYSE450. Our in vivo experiment also showed that metformin markedly inhibited KYSE450 xenograft tumors growth compared to those treated with normal saline. What's more, no obvious toxic reactions were observed. To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo. During the therapy of cancer, in order to overcome side effects, combination therapy was often used. In this paper, we demonstrated that metformin potentiated the effects of cisplatin via inhibiting cell proliferation and promoting cell apoptosis. Taken together, metformin owned the potential anti-cancer effect on ESCC in monotherapy or was combined with cisplatin and these results laid solid basis for the use of metformin in ESCC

Effects of metformin on the proliferation and apoptosis ability of KYSE 450 cells.

<p>A. KYSE 450 cells treated with 5, 10, 20 and 40mmol/L metformin for 24, 48, 72h and cell proliferation was measured by MTT assay. The results revealed that the inhibition rate of the proliferation ability of KYSE 450 cells increased significantly with the time going and concentration rising. *P<0.01 denotes a significant difference between different concentration at the same time point; **P<0.05 denoted a significant difference between different time point at the same concentration. B. Annexin V-FITC/PI was used to analyze of apoptosis ability of KYSE 450 cells treated with 0, 5, 10 and 20 mmol/L metformin. With the increase of concentration, the percentage of apoptotic cells improved markedly. a was the control group, b-d were the group of 5, 10, 20 mmol/L metformin respectively. **P<0.05 denoted a significant difference between different concentration.</p

Metformin inhibited tumor growth in vivo.

<p><b>A.</b>KYSE 450 xenograft treated with metformin (35.75 mg/kg/d) for 15 days were smaller than those treated with normal saline. <b>B.</b> Tumor volume were significantly reduced in metformin treated group than control group. ***P < 0.0001, denoted a markable difference between the size and volume of tumor-bearing nude mice of control group and metformin group. <b>C.</b> HE stain showed that the area of necrosis in xenograft tumors derived from metformin treated group were about 50% larger than those derived from control group.</p

Metformin inhibited 4EBP1 and S6K1 expression in vivo.

<p>Xenograft tumors were harvested, fixed and paraffin-embedded, and stained for 4EBP1, S6K1, p-4EBP1 and p- S6K1 by immunohistochemistry. The protein expression of 4EBP1 and S6K1 were mainly located in the nuclear and cytoplasm of the KYSE450 cells. Immunohistochemical examination exhibited decreased average density of stain for 4EBP1 and S6K1 in metformin treated group than those in control group. The protein expression of p-4EBP1 and p-S6K1 were mainly located in the nuclear of the KYSE450 cells. And the immunohistochemical examination exhibited decreased average density of stain for p-4EBP1 and p-S6K1 in metformin treated group than those in control group. <b>A.</b> The protein expression of 4EBP1 in metformin group (a) and control group (b). <b>B.</b> The protein expression of S6K1 in metformin group (a) and control group (b). <b>C.</b> The protein expression of p-4EBP1 in metformin group (a) and control group (b). <b>D.</b> The protein expression of p-S6K1 in metformin group (a) and control group (b).</p

Metformin treatment inhibited the expression of 4EBP1 and S6K1.

<p><b>A</b>. KYSE 450 cells were treated with 5, 10, 20 mmol/L of metformin for 48h. RT-PCR and western blot results showed that with the increase of concentration, the mRNA and protein expression of 4EBP1and S6K1 decreased significantly compared to those untreated KYSE 450 cells. Furthermore the protein expression of phosphorylated form of 4EBP1 and S6K1 were also inhibited by metformin in a dose dependent manner. <b>B.</b> KYSE 450 cells were treated with 20 mmol/L of metformin for 24, 48 and 72h respectively. RT-PCR and western blot results showed that with the extension of time, the mRNA and protein expression of 4EBP1and S6K1 also decrease greatly compared to those untreated KYSE 450 cells. In addition, the the protein expression of phosphorylated form of 4EBP1 and S6K1 were also inhibited by 20 mmol/L metformin in a time dependent manner. *P < 0.05 denoted a great different effects of different concentrations, different time of metformin on the 4EBP1 and S6K1 mRNA, protein or phosphorylated form of protein expression for esophageal cancer cells KYSE450.</p