Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.     

Integration,visualization and analysis of human interactome

Data integration and visualization are crucial to obtain meaningful hypotheses from the diversity of ‘omics’ fields and the large volume of heterogeneous and distributed data sets. In this review we focus on network analysis as a key technique to integrate, visualize and extrapolate relevant information from diverse data. We first describe challenges in integrating different types of data and then focus on systematically exploring network properties to gain insight into network function. We also describe the relationship between network structures and function of elements that form it. Next, we highlight the role of the interactome in connecting data derived from different experiments, and we stress the importance of network analysis to recognize interaction context-specific features. Finally, we present an example integration to demonstrate the value of the network approach in cancer research, and highlight the importance of dynamic data in the specific context of signaling pathways.     

miR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151

Gastric cancer (GC) is the second common cause of cancer-related death worldwide. microRNAs (miRNAs) play important roles in the carcinogenesis of GC. Here, we found that miR-22 was significantly decreased in GC tissue samples and cell lines. Ectopic overexpression of miR-22 remarkably suppressed cell proliferation and colony formation of GC cells. Moreover, overexpression of miR-22 significantly suppressed migration and invasion of GC cells. CD151 was found to be a target of miR-22. Furthermore, overexpression of CD151 significantly attenuated the tumor suppressive effect of miR-22. Taken together, miR-22 might suppress GC cells growth and motility partially by inhibiting CD151.     

不同能量供需下雌性棕色田鼠胃运动的变化

用PowerLab/8sp生理信号采集分析系统记录哺乳雌鼠、禁食1d和3d雌鼠及正常对照雌鼠胃内压、胃收缩幅值及收缩频率,以研究在不同能量需求与供应状态下,棕色田鼠(Lasiopodomys mandarinus)胃运动的适应性变化。结果显示,禁食组和哺乳期雌鼠的胃内压及胃收缩幅值均显著高于正常对照雌鼠组(P0.05),禁食组胃内压、胃收缩幅值较哺乳组有所下降,且禁食3d组胃内压明显下降(P0.05)。说明在不同生理状态下,能量需求与供应不同,消化道活动发生适应性变化,且消化道生理功能变化与能量胁迫程度相关。     

Proteomic analysis of human gastric juice: a shotgun approach

Gastric juice is the most proximal fluid surrounding the stomach tissue. The analysis of gastric juice protein contents will thus be able to accurately reflect the pathophysiology of the stomach. This biological fluid is also a potential reservoir of secreted biomarkers in higher concentration as compared to the serum. Unlike the rest of the gastrointestinal fluids, there were very few studies reported on gastric juice proteome. To date, the proteins that routinely populate this biofluid are largely unknown. This is partly due to the technical difficulties in processing a sample that contains a collection of other gastrointestinal fluids, especially saliva. In this study, we attempt to profile the protein components of the gastric fluids from chronic gastritis patients using a direct shotgun proteomics approach. These data represent the first report of the proteome of human gastric juice with gastritis background.     

胃癌细胞高尔基体的蛋白质组学技术平台的建立

采用蔗糖密度梯度超速离心法分离纯化高尔基体,双向凝胶电泳（2-DE）分离高尔基体蛋白质,用ImageMaster 2D软件分析所得图谱,基质辅助激光解吸离子化飞行时间质谱(MALDI—TOF MS)鉴定蛋白质点等一系列亚细胞器蛋白质组学方法建立胃癌细胞内高尔基体的蛋白图谱。结果显示分离出的纯度较高的高尔基体建立了分辨率和重复性均较好的双向电泳图谱,运用质谱技术鉴定出12个蛋白质,包括蛋白合成相关蛋白、膜融合蛋白、调节蛋白、凋亡相关蛋白、运输蛋白、细胞增殖分化相关蛋白。通过亚细胞器分离纯化,双向电泳的蛋白分离及MALDI-TOF MS蛋白鉴定分析,首次成功建立了胃癌细胞SGC7901中高尔基体的蛋白质组学技术路线,为胃癌细胞内高尔基体功能的深入研究奠定了基础。     

TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation.Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown.Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGFβ enhanced gastric cancer cell growth and ADAM inhibitors suppressed this effect. EGFR phosphorylation, HB-EGF-CTF nuclear translocation, and cell growth were suppressed in ADAM17 knockdown cells.Conclusion: HB-EGF-CTF nuclear translocation and EGFR transactivation from proHB-EGF shedding mediated by ADAM17 activated by TGFβ might be an important pathway of gastric cancer cell proliferation by TGFβ.     

Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.     

慢性溴氰菊酯摄取对大鼠胃黏膜损伤及P物质的表达的影响

目的:探索溴氰菊酯慢性中毒对大鼠胃黏膜的病理损伤及损伤后P物质表达的影响.方法:实验组大鼠分别给予不同荆量溴氰菊酯灌胃,对照组仅给予橄榄油.取胃体部组织,制成石蜡切片,HE及免疫组织化学染色,镜下观察胃黏膜损伤及胃黏膜组织P物质的表达情况,并对损伤程度进行累计积分、壁细胞计数.结果:高剂量组大鼠胃粘膜慢性损害病理积分与各组相比差异均有显著性(P＜0.05);壁细胞计数与对照组相比较其差异有P＜0.05).免疫组化发现SP在实验组大鼠胃黏膜组织中呈强阳性表达,在对照组则呈弱阳性表达;平均光密度(OD)值显示高、中剂量组之间及与其余各组之间差异均有显著(P＜0.05l.结论:溴氰菊酯对大鼠胃黏膜有较明显的慢性损伤,SP可能参与胃黏膜局部病变.