LncRNA TCF7在胃癌中的表达及与临床病理参数和预后的关系

目的:探讨长链非编码RNA TCF7（LncRNA TCF7）在胃癌中的表达及其与患者临床病理参数和预后的关系。方法:选取2015年2月至2016年8月本院收治的86例胃癌患者的癌组织标本为胃癌组，另选取其癌旁组织为正常组。采用实时荧光定量PCR（RT-PCR）检测胃癌组织及癌旁组织中LncRNA TCF7的相对表达量，根据检测结果中位值将其分为高表达组（57例）与低表达组（29例），观察LncRNA TCF7表达与患者临床病理参数的关系。采用Kaplan-Meier法分析LncRNA TCF7表达与患者预后的关系，并将影响胃癌患者预后的相关因素进行单因素分析及COX多因素分析。结果:胃癌组LncRNA TCF7表达水平显著高于正常组（P＜0.05）；LncRNA TCF7表达与淋巴结转移、临床分期、分化程度及浸润深度显著相关（P＜0.05）；Kaplan-Meier法分析显示LncRNA TCF7高表达组患者PFS与OS均显著低于低表达组（P＜0.05）；单因素分析显示淋巴结转移、临床分期、分化程度、浸润深度及LncRNA TCF7表达水平均为影响胃癌患者预后的危险因素；COX多因素分析显示淋巴结转移与LncRNA TCF7表达水平高低均为胃癌患者预后不良的独立危险因素。结论:LncRNA TCF7在胃癌中高表达，并与胃癌发生发展有关，同时可有效预测患者预后情况。     

HIF-1α与HIF-2α在胃癌中的表达及临床意义

目的:检测缺氧诱导因子-1α(hypoxia inducible factor-1,HIF-1α)和缺氧诱导因子-2α(hypoxia inducible factor-2,HIF-2α)在胃癌中的表达,分析其在癌和癌旁组织中的表达差异,并探讨其与胃癌临床病理特征的关系.方法:收集62例胃癌患者术后癌组织及癌旁组织,采用免疫组织化学染色及Western blot方法检测HIF-1α和HIF-2α的蛋白表达水平,并分析两者的相关性及其与胃癌临床病理的关系.结果:免疫组化结果显示,胃癌组织中HIF-1α 和HIF-2α 的表达均较癌旁组织明显上调,差异有统计学意义(P<0.05);Western blot检测发现胃癌组织中HIF-1α 和HIF-2α 蛋白表达水平均明显高于癌旁组织.相关分析发现HIF-1α在胃癌组织中的高表达与T分期、肿瘤直径及胃癌不同发病部位有显著相关,并且多元Logistic回归分析显示,均为HIF-1α表达异常的独立相关因素(P<0.05);HIF-2α在胃癌组织中的高表达与T分期、肿瘤直径和淋巴结转移显著相关(P<0.05);HIF-1α与HIF-2α在胃癌患者组织中的高表达并无明显相关.结论:HIF-1α和HIF-2α在胃癌组织中异常表达,但无明显相关;提示两者可能存在不同的生理功能和调控机制.     

丝氨酸/精氨酸富有剪接因子1、核因子κB在前列腺癌中的表达及与患者临床特征的关系

目的探讨前列腺癌组织中丝氨酸/精氨酸富有剪接因子1(SRSF1)、核因子κB(NF-κB)的表达情况及与患者临床特征的关系。方法选取前列腺癌患者和前列腺良性增生患者,各70例,取前列腺癌组织和前列腺良性增生组织。免疫组化法检测前列腺癌组织和前列腺良性增生组织SRSF1、NF-κB蛋白的阳性表达率,并分析不同临床特征前列腺癌患者前列腺癌组织中SRSF1、NF-κB蛋白的表达情况。结果前列腺癌组织中SRSF1、NF-κB蛋白的阳性表达率均高于前列腺良性增生组织,差异均有统计学意义(P﹤0.05)。不同前列腺特异性抗原(PSA)水平前列腺癌患者前列腺癌组织中SRSF1蛋白的阳性表达率比较,差异无统计学意义(P﹥0.05);不同TNM分期、淋巴结转移情况、Gleason评分前列腺癌患者前列腺癌组织中SRSF1蛋白的阳性表达率比较,差异均有统计学意义(P﹤0.05)。不同PSA水平、Gleason评分前列腺癌患者前列腺癌组织中NF-κB蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05);不同TNM分期、淋巴结转移情况前列腺癌患者前列腺癌组织中NF-κB蛋白的阳性表达率比较,差异均有统计学意义(P﹤0.05)。结论前列腺癌组织中的SRSF1、NF-κB蛋白表达水平和阳性表达率均较高,SRSF1蛋白的表达可能与TNM分期、淋巴结转移情况和Gleason评分,NF-κB蛋白的表达可能与TNM分期和淋巴结转移情况有关。     

细胞周期调控因子在胃癌组织中的表达及意义

背景与目的细胞周期调控异常与细胞过度增殖及肿瘤发生密切相关,而细胞周期调控因子与胃癌的关系尚未明确。本研究目的是探讨细胞周期调控因子P16INK4、CyclinD1、P21WAF1、P53在胃癌组织中的表达及意义。方法运用免疫组织化学SP法检测53例胃癌及癌旁组织中细胞周期调控因子P16INK4、CyclinD1、P21WAF1、P53的表达。采用多变量Cox回归模型对影响预后的因素进行分析。结果P53蛋白在胃癌组织中的阳性率为60.4%,显著高于癌旁组织(0%)(P<0.01);P53蛋白表达在粘液癌(0%)与高分化腺癌(65.4%)和低分化腺癌(68.2%)间有显著性差异(P<0.01)。CyclinD1蛋白在胃癌组织中的过表达率为69.8%,显著高于癌旁组织(5.7%)(P<0.01)。P16INK4蛋白在胃癌组织中的阳性率为60.3%,显著低于癌旁组织(88.6%)(P<0.05)。P21WAF1蛋白在胃癌组织中的阳性率为26.4%,显著低于癌旁组织(56.6%)(P<0.01)。P16INK4表达与胃癌浸润深度及淋巴结转移相关(分别为P<0.05,P<0.01)。多因素Cox回归分析表明,淋巴结转移、P16INK4为独立预后因素。结论P16INK4蛋白、P21WAF1蛋白低表达和CyclinD1蛋白、P53过度表达与胃癌发生发展有关;P16INK4蛋白的低表达与胃癌浸润、转移及预后有一定关系。     

CHI3L1、Cdc42在胃癌组织中的表达及临床意义

目的 研究壳多糖酶3样蛋白1(CHI3L1)、Cdc42蛋白(Cdc42)在胃癌组织中的表达及临床意义。方法 选取80例原发性胃癌患者的研究对象，患者均未接受放疗或化疗，手术提取患者胃癌组织及癌旁5 cm处正常组织，进行相应实验室检测，比较CHI3L1、Cdc42在胃癌组织及癌旁组织中的表达差异，对胃癌患者性别、年龄、肿瘤部位、直径、浸润深度、淋巴结转移、肿瘤分期等临床病理参数进行比较，分析CHI3L1、Cdc42的阳性表达与其临床病理参数的关系，分析CHI3L1、Cdc42在胃癌组织中的表达及临床意义。结果 CHI3L1、Cdc42在胃癌及癌旁组织中均有阳性表达，胃癌组织中CHI3L1、Cdc42的阳性表达率显著高于癌旁组织(P<0.05)。CHI3L1的阳性表达与胃癌患者肿瘤浸润深度、淋巴结转移呈正相关(P<0.05);Cdc42的阳性表达与胃癌患者肿瘤浸润深度、淋巴结转移、肿瘤分期呈正相关(P<0.05)。结论 CHI3L1、Cdc42在胃癌组织中不同程度的表达与胃癌的发生、发展关系密切，胃癌浸润深度、淋巴结转移越严重，CHI3L1、Cdc42阳性表达越高，临床...     

过氧化酶增殖因子活化受体对胃癌组织中血管内皮生长因子C的调节作用

目的:探讨过氧化酶增殖因子活化受体(peroxisome proliferator-activated receptor gamma,PPARγ)和血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)在胃癌组织中的表达及其相关性。研究PPARγ受体激动剂罗格列酮(rosiglitazone,ROS)对VEGF-C的调节作用。方法:选取经病理证实为胃癌的手术切除石蜡标本60例,同时选取相同病例的癌旁组织,癌旁正常组织作为对照,采用免疫组化法检测PPARγ和VEGF-C表达,分析其与临床病理特征的关系。采用免疫印迹法观察不同浓度的罗格列酮作用于MKN-45胃癌细胞48 h时VEGF-C蛋白表达的变化。结果:免疫组化提示PPARγ阳性率在胃癌中是68.33%,癌旁组织中是51.67%,癌旁正常组织中是20%,三者表达差异有统计学意义(P=0.00);VEGF-C阳性率在胃癌中是63.33%,癌旁组织中是45%,癌旁正常组织中是23.33%,三者表达差异有统计学意义(P=0.00);PPARγ的蛋白表达与VEGF-C表达为负相关(r=-0.897,P=0.000);2者的表达均与胃癌淋巴结转移及TNM分期有关(均P<0.05)。West-blot结果提示选择12.5μmol/L,25μmol/L,50μmol/L,100μmol/L四个浓度的ROS,VEGF-C/β-actin灰度比分别为:0.42,0.35,0.33,0.32,抑制率分别为:57.8%,64.6%,66.6%,68%,对VEGF-C蛋白表达差别具有统计学意义,(P=0.000)。随着PPARγ配体浓度的增加,对VEGF-C的抑制作用增强。β-actin表达在各组中无明显差异。结论:胃癌组织中PPARγ和VEGF-C呈高表达,联合检测这2个指标对评估胃癌浸润转移及判断病情、监测预后有重要意义。PPARγ可能通过抑制VEGF-C的表达而阻止胃癌的淋巴转移。     

音猬因子、Ptch1基因在胃癌中的表达及临床意义

目的:研究胃癌组织中音猬因子（Shh）、Patched1(Ptch1)基因的表达及意义。方法:采用反转录-聚合酶链反应(RT-PCR)和Westem blot检测98例胃癌组织和配对的癌旁组织中Shh、Ptch1 mRNA和蛋白的表达情况。结果:RT-PCR检测结果显示,Shh、Ptch1 mRNA在胃癌中相对表达量分别为0.687±0.057、0.594±0.046,在胃癌旁组织中分别为0.314±0.025、0.293±0.074（P＜0.05）。Western blot检测结果显示,Shh、Ptch1蛋白在胃癌中的相对表达量分别为0.525±0.057、0.481±0.046,在胃癌旁组织中分别为0.236±0.025、0.215±0.074。胃癌组织Shh、Ptch1 mRNA和蛋白平均表达水平高于癌旁组织,差异有统计学意义（P＜0.05）;Shh、Ptch1 mRNA和蛋白表达水平与胃癌的分化程度、TNM分期、浸润深度和淋巴结转移明显相关（P＜0.05）,与患者年龄、性别和肿瘤直径无明显相关（P＞0.05）。结论:胃癌组织中Shh、Ptch1蛋白呈高表达,Shh、Ptch1蛋白的高表达可能与胃癌的发生及发展有关。     

胃癌组织转录调节因子DEC1表达及其临床意义的研究

目的:探讨转录调节因子DEC1在人胃癌组织中的表达以及临床意义.方法:应用RT-PCR和蛋白质印迹法技术检测多种胃癌细胞株中DEC1的表达.运用免疫组化技术检测52例胃癌组织及10例癌旁胃黏膜组织中DEC1的表达.结果:在正常的胃黏膜上皮细胞株GES1及多种胃癌细胞株中均能检测到DEC1 mRNA的表达,但胃癌细胞株中(MKN28、SGC 7901、MGC 803和HGC27)的表达显著高于胃黏膜上皮细胞株GES1.蛋白质印迹法显示DEC1在蛋白水平的结果与前一致.DEC1在胃癌组织、癌旁胃黏膜组织中表达阳性率分别为55.77%、10.00%,DEC1蛋白的表达水平与胃癌的分化程度相关,P<0.05.与患者性别、年龄、肿瘤大小、肿瘤类型、TNM分期和有无淋巴结转移均无关,P>0.05.结论:DEC1在各种类型的人胃癌细胞和胃癌组织中都有较高的表达,可能在胃癌的发生、发展中起重要的作用.     

胃癌组织中基质细胞因子-1及其受体的表达及临床意义

目的探讨基质细胞衍生因子-1(SDF-1)及其受体CXCR4在胃癌组织中的表达及其临床意义。方法应用免疫组化Envision两步法检测80例胃癌患者的胃癌组织及癌旁组织中SDF-1和CXCR4的表达。结果胃癌组织中SDF-1和CXCR4的阳性表达率分别为85.0%和61.3%,高于癌旁组织的46.3%和28.8%,差异有统计学意义(P<0.05)。SDF-1与CXCR4的表达呈正相关,SDF-1和CXCR4的表达水平与胃癌患者的病理分期、淋巴结转移、组织学分级相关(P<0.05)。结论胃癌组织中SDF-1、CXCR的表达水平与病理分期、淋巴结转移、组织学分级密切相关,可作为胃癌诊断和预后的免疫病理学指标,有望成为药物治疗胃癌的靶点。     

组织因子与肿瘤

近年来认为肿瘤的血管生成、侵袭和转移与凝血高度相关,其中一个关键蛋白就是组织因子（TF）。TF可作为细胞内信号传导介质,改变基因表达形式和细胞行为,明确参与肿瘤相关性血管生成,其表达量与多种肿瘤转移相关。抗血管生成和TF靶向治疗阻止肿瘤生长和转移,有望成为一种新的抗肿瘤治疗方法。     

组织因子与肿瘤

近年来认为肿瘤的血管生成、侵袭和转移与凝血高度相关,其中一个关键蛋白就是组织因子(TF)。TF可作为细胞内信号传导介质,改变基因表达形式和细胞行为,明确参与肿瘤相关性血管生成,其表达量与多种肿瘤转移相关。抗血管生成和TF靶向治疗阻止肿瘤生长和转移,有望成为一种新的抗肿瘤治疗方法。     

Levels of vascular endothelial growth factor,hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis

Angiogenesis is a possible target in the treatment of human gliomas. To evaluate the role of 3 growth factors, vascular endothelial growth factor (VEGF), hepatocyte growth factor/scatter factor (HGF/SF) and basic fibroblast growth factor (bFGF), in the angiogenic cascade, we determined their levels in extracts of 71 gliomas by enzyme‐linked immunosorbent assay (ELISA). The levels of bFGF were only marginally different between gliomas of World Health Organization (WHO) grade II (low grade) and grades III and IV (high grade). In contrast, the mean concentrations of VEGF were 11‐fold higher in high‐grade tumors and those of HGF/SF 7‐fold, respectively. Both were highly significantly correlated with microvessel density (p < 0.001) as determined by immunostaining for factor VIII‐related antigen. In addition, VEGF and HGF/SF appeared to be independent predictive parameters for glioma microvessel density as determined by multiple regression analysis. We measured the capacity of all 3 factors to induce endothelial tube formation in a collagen gel. In this assay, bFGF was found to be an essential cofactor with which VEGF as well as HGF/SF were able to synergize independently. According to the concentrations of angiogenic factors, extracts from high‐grade tumors were significantly more potent in the tube formation assay than the low‐grade extracts (p = 0.02). Adding neutralizing antibodies to bFGF, VEGF and HGF/SF together with the extracts, tube formation was inhibited by up to 98%, 62% and 54%, respectively. Our findings suggest that bFGF is an essential cofactor for angiogenesis in gliomas, but in itself is insufficient as it is present already in the sparsely vascularized low‐grade tumors. Upon induction of angiogenesis in high‐grade tumors, bFGF may synergize with rising levels of not only VEGF but possibly also with HGF/SF, which appears here to be an independent angiogenic factor. Int. J. Cancer (Pred. Oncol.) 84:10–18, 1999. © 1999 Wiley‐Liss, Inc.     

Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor.

We have examined levels of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in neoplastic and non-neoplastic bladder tissue using a standard radioimmunoassay technique. Tumour samples had much higher TGF-alpha levels compared with EGF and TGF-alpha levels in malignant tissue were significantly higher than in benign bladder samples. There was, in addition, a difference in mean EGF levels from ''normal'' bladder samples from non-tumour bearing areas of bladder in patients with bladder cancer compared with ''normal'' bladder tissue obtained at the time of organ retrieval surgery. Levels of EGF and TGF-alpha did not correlate with levels of EGF receptor (EGFR) as determined by a radioligand binding method but levels of TGF-alpha > 10 ng gm-1 of tumour tissue did correlate with EGFR positivity defined using immunohistochemistry. These data suggest that TGF-alpha is the likely ligand for EGFR in bladder tumours.     

Assessment of biological activity of linear alpha-transforming growth factor and monospecific antibodies to alpha-transforming growth factor and linear alpha-transforming growth factor

alpha-Transforming growth factors (TGFs) are low-molecular-weight polypeptides (Mr 5000-7000) which are secreted by a variety of human cancer cells in vitro. Their presence has also been reported in the urine of patients with malignancies, human tumor extracts, and in the conditioned medium of primary human tumor cell cultures. There is evidence that alpha-TGFs bind to membrane receptors of the secreting cells, thus stimulating cell growth in a positive feedback manner (autocrine secretion). We have used a synthetic linear alpha-TGF to study the biological activity of affinity-purified polyclonal sheep antibodies against the carboxyterminal part (17 amino acids) of synthetic rat alpha-TGF. The antigen was found to bind to epidermal growth factor receptors of target cells and to stimulate soft agarose colony formation of normal fibroblasts. Although the antibodies recognized the linear alpha-TGF molecule, they did not inhibit the binding to epidermal growth factor receptors. The antibodies also failed to inhibit alpha-TGF-stimulated colony formation of normal rat fibroblasts. In addition, essentially no cytotoxic activity of the antibodies was found against 41 fresh human tumor specimens in a human tumor cloning assay. Antibodies against the complete alpha-TGF molecule should be used in further attempts to interfere with the autocrine secretion of transforming growth factors.     

血管内皮生长因子及其受体与骨肉瘤关系的研究进展

血管内皮生长因子（ＶＥＧＦ）是一种序列高度保守、高度特异性的促血管内皮细胞生长因子,广泛分布于人和动物体内的大脑、肾脏、肝脏、脾脏、胰腺和骨骼等组织中,对内皮细胞具有强烈的促有丝分裂作用,刺激血管内皮细胞增殖和血管通透性增加,促进新生血管形成。ＶＥＧＦ通过与血管内皮细胞表面受体（ＶＥＧＦＲ）特异性结合发挥生物学效应。抑制ＶＥＧＦ及ＶＥＧＦＲ的活性可以减缓或阻滞骨肉瘤侵袭和转移。研究表明,ＶＥＧＦ及ＶＥＧＦＲ对肿瘤血管及淋巴管的生成及肿瘤侵袭和转移起重要作用。本文对ＶＥＧＦ及ＶＥＧＦＲ与骨肉瘤血管与淋巴管生成及其侵袭与转移的关系作一综述。     

Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis

The multifunctional growth factor scatter factor/hepatocyte growth factor (SF/HGF) and its receptor tyrosine kinase c-Met have emerged as key determinants of brain tumor growth and angiogenesis. SF/HGF and c-Met are expressed in brain tumors, the expression levels frequently correlating with tumor grade, tumor blood vessel density, and poor prognosis. Overexpression of SF/HGF and/or c-Met in brain tumor cells enhances their tumorigenicity, tumor growth, and tumor-associated angiogenesis. Conversely, inhibition of SF/HGF and c-Met in experimental tumor xenografts leads to inhibition of tumor growth and tumor angiogenesis. SF/HGF is expressed and secreted mainly by tumor cells and acts on c-Met receptors that are expressed in tumor cells and vascular endothelial cells. Activation of c-Met leads to induction of proliferation, migration, and invasion and to inhibition of apoptosis in tumor cells as well as in tumor vascular endothelial cells. Activation of tumor endothelial c-Met also induces extracellular matrix degradation, tubule formation, and angiogenesis in vivo. SF/HGF induces brain tumor angiogenesis directly through only partly known mechanisms and indirectly by regulating other angiogenic pathways such as VEGF. Different approaches to inhibiting SF/HGF and c-Met have been recently developed. These include receptor antagonism with SF/HGF fragments such as NK4, SF/HGF, and c-Met expression inhibition with U1snRNA/ribozymes; competitive ligand binding with soluble Met receptors; neutralizing antibodies to SF/HGF; and small molecular tyrosine kinase inhibitors. Use of these inhibitors in experimental tumor models leads to inhibition of tumor growth and angiogenesis. In this review, we summarize current knowledge of how the SF/HGF:c-Met pathway contributes to brain tumor malignancy with a focus on glioma angiogenesis.     

Megakaryocyte colony-stimulating factor and thrombopoiesis

Although megakaryocyte differentiation and proliferation is understood to be regulated by "humoral" factors, the molecular identities of such factors have, until recently, been obscure. The "two factor" model of megakaryocytopoiesis/thrombopoiesis is critically reviewed. In this model, "Megakaryocyte Colony-Stimulating Factor" (Meg-CSF) determines the early differentiational events of megakaryocytopoiesis, and "Thrombopoietin" (Tpo) is held responsible for the maturation of the megakaryocyte and the biochemical/cytological events in platelet formation and release. To date, neither of these growth factors have been molecularly cloned. When this occurs, the clarification of the roles Meg-CSF, Tpo and other secondary modulators (such as IL-3 and GM-CSF) play in platelet formation in health and disease will be made manifest.