RELATIONSHIP OF THE EXPRESSION OF MDR1 GENE PRODUCT IN HEPATO CELLULAR CARCINOMA TO INVASION AND METASTASIS

ＩＮＴＲＯＤＵＣＴＩＯＮＰｇｌｙｃｏｐｒｏｔｅｉｎ（Ｐｇｐ），ｔｈｅｐｒｏｄｕｃｔｏｆｔｈｅｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ（ＭＤＲ１）ｇｅｎｅ，ｉｓａ１７０Ｋｄａｍｅｍｂｒａｎｅｐｒｏｔｅｉｎｒｅｓｐｏｎｓｉｂｌｅｆｏｒｐｕｍｐｉｎｇ...     

基质金属蛋白酶与前列腺癌的相关探讨

MMPs是一类依赖锌的胞外水解酶,可降解细胞外基质,从而促进肿瘤侵袭和转移.TIMPs是MMPs内源特异性组织抑制因子.几乎能够抑制所有MMPs活性.大量研究发现MMPs和TIMPs的活性比值与肿瘤侵袭和转移相关.前列腺癌是男性泌尿生殖系肿瘤中极易发生侵袭和转移的一种恶性肿瘤.有研究认为MMPs及TIMPs在前列腺癌的侵袭及转移中起重要作用,有关MMPs的研究与前列腺癌的预防、诊断和治疗密切相关,部分已经应用于临床治疗.     

肺癌细胞在缺氧状态下体外侵润力的变化及分子基础

目的 探讨缺氧对肺癌细胞体外侵润力的影响及其分子基础。方法 将小细胞肺癌细胞H128分别置于常氧、低氧和无氧环境中培养48h后，用羊膜内皮细胞模型测定各组细胞的侵润能力。同时测定并分析了上皮钙粘附素、β1-整合素的表达量。结果 与常氧组相比，低氧组细胞侵润能力显著高于常氧组。低氧组E-钙粘附素表达显著降低及β1-整合素表达量显著增强，无氧组两者均显著降低。结论 适度缺氧可以下调肺癌细胞表达E-钙粘附素，增加β1-整合素表达，增强癌细胞侵润力。但是严重缺氧使癌细胞粘附分子表达及细胞侵润力均下降。     

microRNA启动子区甲基化调控对人肺癌细胞A549增殖、迁移、侵袭的影响

目的研究microRNA启动子区甲基化水平的变化对几种microRNAs（miRNA34a、miRNA34b、miRNA148a、miRNA203a）表达的影响,并进一步研究该甲基化调控对人肺癌细胞A549增殖、迁移以及侵袭能力的影响。方法不同浓度的去甲基化药物5-氮杂-2′-脱氧胞苷（5-Aza-CdR) 处理人肺癌细胞A549,分别作用24 h、48 h、72 h,采用CCK8法检测细胞增殖情况,计算增殖抑制率。20 μmol/L 5-Aza-CdR处理A549细胞72 h,通过甲基化特异性PCR(MSP)检测A549细胞相关miRNAs启动子甲基化水平的变化;实时荧光定量PCR(real-time PCR)检测A549细胞相关miRNAs表达水平的变化。20 μmol/L 5-Aza-CdR处理A549细胞0 h、24 h、48 h,采用划痕实验检测细胞迁移能力（计算细胞在24 h和48 h的划痕愈合率）;作用48 h,采用Transwell检测细胞侵袭能力。结果CCK8结果显示,随着5-Aza-CdR的处理浓度升高、时间延长,A549细胞的增殖抑制率逐渐增加。经5-Aza-CdR去甲基化处理后,MSP结果表明,实验组相对于对照组甲基化引物扩增条带减弱,而非甲基化引物扩增条带增强;Real-time PCR结果显示,相关miRNAs表达水平升高（P<0.05）。由划痕实验和Transwell检测结果揭示,经5-Aza-CdR处理后,A549细胞的生长愈合能力降低（P<0.05）,并且侵袭到Transwell小室滤膜下表面的细胞数亦减少（P<0.05）。结论人肺癌细胞A549经5-Aza-CdR去甲基化处理后,miRNAs表达水平升高,进一步抑制肺癌细胞的增殖、迁移以及侵袭能力。     

miR-155反义寡核苷酸转染对人大肠癌Lovo细胞侵袭的影响

目的探讨miR-155对人大肠癌细胞侵袭能力的影响。方法大肠癌Lovo细胞分为3组：脂质体介导反义miR-155（AS-miR-155）组、无义寡脱氧核苷酸（ODN）组和对照组。测定荧光素酶活性验证3组细胞中miR-155的表达,采用Matrigel基质生长试验检测细胞生长情况,以Transwe Ⅱ方法检测细胞的侵袭力,结果与对照组和无义ODN组比较,转染AS-miR-155组Lovo细胞miR-2l表达水平降低;Matrigel基质生长试验显示,转染AS-miR-155组Lovo细胞体外培养克隆平均直径较小,Transwe Ⅱ细胞侵袭试验显示转染AS-miR-155组穿膜细胞数较少。结论 miR-2l高表达可促进Lovo大肠癌细胞侵袭生长,提示miR-155可以作为基因治疗大肠癌的候选靶点。     

Impact of 3′UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population

ObjectiveSeveral studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3′ untranslated region (3′UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3′UTR regions of the KRAS gene and the effect of KRAS 3′UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT.MethodsCodons 12, 13, and 61 and 3′UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients.ResultsWe defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3′UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.     

STEAP1 Inhibits Breast Cancer Metastasis and Is Associated With Epithelial–Mesenchymal Transition Procession

Purpose

Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell surface antigen overexpressed in multiple cancers and is associated with malignancy and disease prognosis. The aims of this study were to evaluate STEAP1 expression in breast cancer and to determine the mechanisms involved.

MicroRNA-93 promotes bladder cancer proliferation and invasion by targeting PEDF

Objective

MicroRNA-93 (miR-93) is upregulated in the urine of patients with bladder cancer (BC). Here, we investigated the role of miR-93 in BC progression and explored the underlying mechanism.