Periostin Mediates the Increased Pro‐Angiogenic Activity of Gastric Cancer Cells under Hypoxic Conditions

This study was conducted to investigate the biological role of periostin in gastric cancer (GC) under hypoxia. Western blot analysis revealed that along with an upregulation of hypoxia‐inducible factor‐1alpha, there was a time‐dependent induction of periostin in MKN‐45 cells under hypoxia (2% O₂), increasing by eightfold as compared to normoxic cells. Pretreatment with 30 µM PD98059, an inhibitor of ERK1/2, significantly reduced hypoxia‐stimulated periostin expression (P < 0.01). Periostin knockdown in MKN‐45 cells was achieved by specific small interfering RNA (siRNA). The conditioned medium from periostin siRNA‐transfected MKN‐45 cells induced significantly less (P < 0.01) endothelial tube formation than control siRNA‐transfected cells. Additionally, periostin silencing markedly decreased the mRNA expression and secretion of vascular endothelial growth factor (VEGF) in hypoxic MKN‐45 cells. Thus, our data suggest that periostin is a hypoxia‐response gene and mediates a cross talk between GC and endothelial cells under hypoxia, partially through regulation of the VEGF expression. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:364‐369, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21498     

Genotyping of IL-8-251 T > A yields prognostic information in patients with gastric carcinoma

Abstract

This study was designed to investigate the association of the IL-8-251?T?>?A gene polymorphism with clinicopathological features and the prognostic role of the gene polymorphism in patients with gastric adenocarcinoma. The gene polymorphism was detected by the polymerase chain reaction–restriction fragment length polymorphism method, followed by univariate and multivariate analyses to elicit its prognostic role. The frequency of IL-8-251?A/A, A/T and T/T genotypes were 11.0% (23/210), 43.8% (92/210) and 45.2% (95/210), respectively. The IL-8-251 gene polymorphism was closely correlated with depth of invasion (p?=?0.007), grade of differentiation (p?=?0.002) and TNM stage (p?=?0.009). A/A genotype carriers showed more frequency of serosa involvement, low grade of differentiation and advanced stage of gastric carcinoma. IL-8-251?T?>?A gene polymorphism have no significant correlation with other clinicopathological features. The 5-year overall survival of IL-8-251?A/A genotype and T allele carriers were 30.8% and 59.2%, respectively. There is a significant discrepancy among the different genotype carriers. Multivariate analysis with the Cox regression model revealed that the IL-8-251?A/A genotype is an independent prognostic indicator (HR?=?2.285, 95% Confidence Interval?=?1.06–4.93, p?=?0.035). We conclude that the IL-8-251?A/A genotype may indicate a poor prognosis for gastric adenocarcinoma patients.     

外周血树突状细胞CD83＋表达对胃癌术后病人预后影响及意义

目的：探讨胃癌外周血中树突状细胞CD83＋表达对预后的影响及意义。方法：选取2010年1月至2011年6月间我科收治的胃癌病人74例进行分析,均为原位癌或仅有局部淋巴结转移,以外周血树突状细胞CD83＋为研究对象,以术后生存时间为标准,对病人手术预后进行分析。结果：所选74例病人术后3周测得外周血树突状细胞CD83＋表达频数平均值（7．32＋1．88脚,以表达频数中位数7．32％为标准将74例病人分为高频组和低频组两组,每组37人。术后总体生存时间108周-413周,平均生存时间（207＋227）周,其中高值组平均生存时间（247＋121）周,低值组平均生存时间（118＋54）周,两组生存时间具有明显差别（P〈O．05）。结论：胃癌外周血中树突状细胞CD83＋的表达对接受手术病人预后有重要影响,可以作为判断病人预后的参考依据,对预后不良者加以对症及时干预以降低死亡率。     

Reglα蛋白表达在胃癌及癌前病变组织中的变化

目的：观察再生基因1α（Regeneration gene 1α,Regla）在胃癌前病变组织及胃癌组织中的表达变化,探讨Reglot在胃粘膜癌变中发挥的作用,为临床诊治提供理论基础。方法：收集2011年1月-2012年12月在我院接受胃镜活检的患者胃粘膜组织,病理确诊为浅表性胃炎的为正常组,中度以上萎缩及肠化的为癌前病变组及胃腺癌即胃癌组。采用荧光定量PCR的方法检测三组胃粘膜组织中Regla的mRNA表达情况。结果：Reglet的mRNA表达在正常组、癌变组及胃癌组织中呈进行性升高;胃癌组中,低分化及印戒细胞癌和Ⅳ期胃癌患者的Reg1α表达升高最为明显;Regla在不同分化程度的胃癌组织间表达无显著差异;Regla在Ⅳ期胃癌中的表达显著高于I／II期;差异均具有统计学意义（P〈0．05）。结论：作为一种生长因子Regla可能参与了胃粘膜癌变的过程,并且Reglet的高表达可能与胃癌的预后相关。     

HIF-1α和VEGF—c在胃癌组织中的表达及临床意义研究

目的：探讨HIF-1α和VEGF—c在胃癌组织中的表达情况及临床病理意义。方法：选取2010年12月至2012年12月期间就诊于我院肿瘤外科需进行手术切除的胃癌标本及其配对的癌旁组织各73例进行研究分析,采用免疫组化SP（streptavidin perotridase）对胃癌组织以及癌旁组织中HIF-1α和VEGF-c的表达情况进行检测。结果：①HIF-1α和VEGF-c在癌旁组织几乎不表达,而在胃癌组织中的阳性表达率分别为83．56％、78．08％,显著高于癌旁组织,经分析,差异具有统计学意义（P〈0．05）;②HIF—hx和VEGF-c的阳性表达和浸润深度、淋巴结转移以及临床分期密切相关,差异具有统计学意义（P〈0．05）;③HIF-1α和VEGF-c在胃癌组织中的表达存在一定的相关性（r=0．654,P〈0．05）。结论：HIF．hx和VEGF-c的阳性表达可以作为胃癌侵袭转移的重要判定指标,这对于本病的临床治疗具有一定的指导性意义。     

In silico identification of novel lncRNAs with a potential role in diagnosis of gastric cancer

Abstract

Gastric cancer (GC) is the second leading cause of cancer-related deaths in the world. Due to the shortage of adequate symptoms in the early stages, it is diagnosed when the tumor has spread to distant organs. Early recognition of GC enhances the chance of successful treatment. Molecular mechanisms of GC are still poorly understood. LncRNAs are emerging as new players in cancer in both oncogene and tumor suppressor roles. High-throughput technologies such as RNA-Seq, have revealed thousands of lncRNAs which are dysregulated in GC. In this study, we retrieved lncRNAs obtained by High-throughput technologies from OncoLnc database. Consequently, retrieved lncRNAs were compared in literature-based databases including PubMed. As a result, two lists, including experimentally validated lncRNAs and predicted lncRNAs were provided. We found 43 predicted lncRNAs that had not been experimentally validated in GC, so far. Further Bioinformatics analyses were performed to obtain the expression profile of predicted lncRNAs in tumor and normal tissues. Also, the roles and targets of predicted lncRNAs in GC were identified by related databases. Finally, using the GEPIA database was reviewed the significant relationship of predicted lncRNAs with the survival of GC patients. By recognizing the lncRNAs involved in initiation and progression of GC, they may be considered as potential biomarkers in the GC early diagnosis or targeted treatment and lead to novel therapeutic strategies.

Communicated by Ramaswamy H. Sarma     

Association of the variant rs2243421 of human DOC-2/DAB2 interactive protein gene (hDAB2IP) with gastric cancer in the Chinese Han population

Human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumor-suppressor gene that inhibits cell survival and proliferation and induces cell apoptosis. It was reported that the expression level of hDAB2IP in gastric cancer tissue was highly correlated with tumor progression, however, whether hDAB2IP genetic variants are associated with the risk of gastric cancer remains yet unknown. In this case–control study, we conducted a genetic analysis for hDAB2IP variants in 311 patients with gastric cancer and 425 controls from the Chinese Han population. We found that the SNP rs2243421 of hDAB2IP gene with the minor allele C significantly revealed strong association with decreased gastric cancer susceptibility (P = 0.007, adjusted odds ratio [OR] = 0.734, 95%CI = 0.586–0.919). Haplotypes rs2243421 and rs10985332 (HaploType: CC, P = 0.012, aOR = 0.760) and haplotypes rs2243421 and rs555996 (HaploType: CG, P = 0.034, aOR = 0.788) represented the decreased risk of gastric cancer, respectively. On the contrary, rs2243421 and rs555996 showed an elevated susceptibility (HaploType: TG, P = 0.010, aOR = 1.320). Our results for the first time provided new insight into susceptibility factors of hDAB2IP gene variants in carcinogenesis of gastric cancer.     

Effect of menthol in experimentally induced ulcers: Pathways of gastroprotection

Based on ethnopharmacological indications that Mentha species may be used in the treatment of gastrointestinal diseases, this study aimed to characterize the gastroprotective mechanisms of menthol (ME), the major compound of the essential oil from species of the genus Mentha. The gastroprotective action of ME was analyzed in gastric ulcers that were induced by ethanol or indomethacin in Wistar male rats. The mechanisms responsible for the gastroprotective effect were assessed by analyzing the amount of mucus secreted, involvement of non-protein sulfhydryl (NP-SH) compounds, involvement of calcium ion channels and NO/cGMP/K⁺_ATP pathway, gastric antisecretory activity and the prostaglandin E₂ (PGE₂) production. The anti-diarrheal activity and acute toxicity of ME were also evaluated. Oral treatment with ME (50 mg/kg) offered 88.62% and 72.62% of gastroprotection against ethanol and indomethacin, respectively. There was an increased amount of mucus and PGE₂ production. The gastroprotective activity of ME involved NP-SH compounds and the stimulation of K⁺_ATP channels, but not the activation of calcium ion channels or the production of NO. The oral administration of ME induced an antisecretory effect as it decreased the H⁺ concentration in gastric juice. ME displayed anti-diarrheal and antiperistaltic activity. There were no signs of toxicity in the biochemical analyses performed in the rats’ serum. These results demonstrated that ME provides gastroprotective and anti-diarrheal activities with no toxicity in rats.     

Cetuximab enhances TRAIL-induced gastric cancer cell apoptosis by promoting DISC formation in lipid rafts

TRAIL is a member of the tumor necrosis factor family that selectively induces cancer cell apoptosis. However, gastric cancer cells are insensitive to TRAIL. Our and others studies showed that the inhibition of EGFR pathway activation could increase the sensitivity of TRAIL in cancer cells. But the detailed mechanism is not fully understood. In the present study, compared with TRAIL or cetuximab (an anti-EGFR monoclonal antibody) alone, treatment with the TRAIL/cetuximab combination significantly promoted death receptor 4 (DR4) clustering as well as the translocation of both DR4 and Fas-associated death domain-containing protein (FADD) into lipid rafts. This in turn resulted in caspase-8 cleavage and the formation of the death-inducing signaling complex (DISC) in these lipid rafts. Cholesterol-depletion with methyl-β-cyclodextrin partially prevented DR4 clustering and DISC formation, and thus partially reversed apoptosis induced by the TRAIL/cetuximab dual treatment. These results indicate that cetuximab increases TRAIL-induced gastric cancer cell apoptosis at least partially through the promotion of DISC formation in lipid rafts.     

Apport de la tomoscintigraphie au technétium 99 m dans le diagnostic des duplications gastriques de l’enfant : à propos d’un cas

Gastric duplications (GD) are rare congenital digestive malformations of the child. Their diagnosis often involves multiple medical imaging modalities ranging from ultrasound to CT or MRI. Scintigraphy is an excellent diagnostic method rarely used especially when the discovery mode of GD is not associated with gastro-intestinal bleeding. We report a case of a non-communicating and non-hemorrhagic GD discovered in a 6-year-old girl whose exploration has benefited many ways including SPECT imaging after intravenous injection of Tc-99 m pertechnetate. Our goal is to focus on the role of scintigraphy in the diagnostic management of the DG of the child and to discuss the opportunity of the other imaging techniques in the exploration of this pathology.