FHIT和Survivin基因在大肠癌中的表达及意义

应用免疫组织化学S-P法检测59例大肠癌和40例正常大肠粘膜组织FHIT和Survivin基因的表达。结果表明：大肠癌组织FHIT和Survivin表达的阳性率分别为49．2％，45．8％，正常大肠粘膜组织FHIT和Survivin表达的阳性率分别为77．5％，12．5％，二者FHIT和Survivin阳性表达的差异均有显著意义（P〈0．05）；FHIT表达与大肠癌临床分级（P％0．001）、Dukes分期（P％0．001）和淋巴结转移均有关（P〈0．001）。Survivin表达均与大肠癌临床分级、Dukes分期和淋巴结转移无关；在大肠癌中，FHIT和Survivin表达之间呈显著负相关（P〈0．001）。     

PCNA,KI67在胃黏膜良恶性病变中表达的临床研究

目的　探讨增殖细胞抗原PCNA,KI67在胃黏膜良恶性病变中表达的临床意义.方法　采用免疫组织化学方法,对44例胃溃疡恶变的胃癌切除术标本中胃癌组织、周围黏膜及正常黏膜中PCNA,Ki67的表达进行检测,分析细胞的增殖状态及恶性程度.结果　PCNA,Ki67在胃癌组织及癌周组织中均呈现高表达状态,而正常黏膜则呈现低表达,两者均具有显著性差异(P<0.05).结论　PCNA及ki67的表达情况可为高危人群胃黏膜病变的重要诊断指标.     

Suppression of murine breast cancer metastasis by selective inhibition of CXCR4 by synthetic polypeptide derived from viral macrophage inflammatory protein II

Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have been implicated in breast cancer metastasis. A significant association between HER2 and CXCR4 expression has been observed in human breast tumor tissues, and overexpression of CXCR4 is essential for HER2-mediated tumor metastasis. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 may limit tumor metastasis. The present study investigated the action of a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein II against CXCR4 (NT21MP) in inhibiting metastasis in vitro and in vivo. The results showed that chemotaxis of SKBR3 cells toward SDF-1α was reduced by NT21MP in a dose-dependent manner (P < 0.05). NT21MP inhibited tumor growth at 500 μg/kg and in combination with Herceptin, the anti-HER2 antibody. The in vivo metastatic assay showed that NT21MP significantly inhibited pulmonary metastasis, and the number of metastatic tumor nodes on the surface of the lung was greatly decreased. Compared with the saline-treated control group, PCNA expression was dose-dependently decreased by NT21MP, the percentage of apoptotic cells was increased, and CXCR4 mRNA and protein expression were downregulated. In conclusion, NT21MP inhibits cellular prolifer-ation, promotes apoptosis by downregulating CXCR4 expression, and suppresses the progression of primary and metastatic tumors. CXCR4 may be a useful therapeutic target for breast cancer, and NT21MP may serve as a potential target drug for the treatment of breast cancer metastasis.     

The application of Tau protein testing to gastric cancer patients treated with paclitaxel

Paclitaxel is one of the main drugs used to treat gastric cancer, but many tumors develop drug resistance, resulting in treatment failure. The levels of expression of Tan protein in breast tumors have been found to be related to paclitaxel resistance, suggesting that Tau protein expression may predict breast cancer sensitivity to paclitaxel treatment. To determine whether Tan protein ex- pression can predict gastric cancer sensitivity to paclitaxel, we assayed Tan protein expression levels in gastric cancer specimens from 70 patients. We observed Tan protein expression in 54 of 70 （77.1%） specimens. Assays in gastric cancer cell lines showed that Tan protein expression was significantly lower in BGC823 than in MKN45 cells （P -- 0.0147）. MTT assays showed that dif- ferent concentrations of paclitaxel inhibited the growth of MKN45 and BGC823 cells, but inhibition and apoptosis were more obvious in cells expressing low levels of Tau protein. Paclitaxel chemotherapy was effective in 34 of the 70 patients （48.6%） and was significantly correlated with low expression of Tau protein （P 〈 0.01）. These findings indicate that Tau protein is expressed in a high percentage of gastric cancers, with paclitaxel being more effective in tumors with low Tau expression.     

人食管鳞癌及正常食管组织中Notch1基因的mRNA及蛋白的表达

采用RT-PCR方法,分别从人食管鳞癌及正常食管组织中扩增 Notch1基因,结果表明Notch1基因在人食管鳞癌及正常食管组织中均有表达.此外,通过免疫组织化学方法检测不同病理特征的35例食管鳞癌、16例原位癌及35例癌周正常食管粘膜上皮组织Notch1蛋白表达的变化,结果显示:Notch1蛋白在正常食管粘膜上皮组织和原位癌中的阳性率分别为82.9%、68.7%,二者无显著性差异(P＞0.05),但均显著高于食管鳞癌组织37.1%(P＜0.05),食管鳞癌Notch1蛋白的低表达与肿瘤的直径、分期和发生部位无关(P＞0.05),但与淋巴结转移有关(P＜0.05).这表明在正常食管粘膜上皮组织中Notch1蛋白高表达,而在食管癌鳞中Notch1蛋白呈现低表达或不表达.该研究为进一步探明Notch1基因的表达对食管癌细胞的发生、发展的影响奠定了良好的基础.     

大肠癌中MTA1和nm23 - H1蛋白的表达及其意义

目的：探讨大肠癌中MTA1、nm23-H1蛋白的表达及其意义。方法：用免疫组化留法检测84例大肠癌MTA1、nm23-H1蛋白的表达。结果：84例大肠癌中MTA1、nm23-H1阳性表达率分别为61．9％和51．2％;MTA1高表达与大肠癌组织分化程度、Duke’s分期和淋巴结转移关系密切（P〈0．05）;nm23-H1低表达与大肠癌组织分化程度、Duke’s分期和淋巴结转移关系密切（P〈0．05）;大肠癌中MTA1和nm23-H1蛋白表达呈负相关（P〈0．05）。结论：MTA1和nm23-H1蛋白表达与大肠癌分化程度、淋巴结转移和预后密切相关,可作为判断大肠癌患者转移复发的参考指标。     

恶性胸膜间皮瘤中间皮素表达的临床病理相关性及其预后意义

通过探讨间皮素(MSLN)与恶性胸膜间皮瘤临床病理之间的相关性及其预后意义.采用R 3.6.3对美国公共癌症基因数据库(TCGA)进行数据挖掘和分析,利用Oncomine数据库对非癌组织与癌组织中MSLN的表达量进行比较分析,采用基因表达谱动态分析(GEPIA)构建Kaplan-Meier生存模型探究MSLN表达量对恶...     

血管内皮生长因子-C及其受体Flt-4在大肠癌组织中表达的意义

目的：探讨血管内皮生长因子C(VEGF-C)及其Flt-4受体在大肠癌的表达与淋巴管新生及转移的关系。方法：对58例大肠癌组织及12例正常肠黏膜进行VEGF-C、FLt-4及CD34免疫组织化学染色，并计数微淋巴管密度(LMVD)和血管密度(MVD)。结果：VEGF-C在大肠癌中的表达明显高于正常黏膜(P＜O．01)。大肠癌VEGF-C表达与淋巴结转移及Dukes分期呈显正相关(P＜O．01)。大肠癌微淋巴管密度(LMVD)与淋巴结转移呈正相关(P＜O．01)。结论：VEGF-C在大肠癌中表达升高，可能通过旁分泌方式作用于Flt-4信号通路引发淋巴管新生，有助于发生淋巴结转移；VEGF-C对判断大肠癌预后有辅助作用。     

突变型P53蛋白、C-erbB-2癌蛋白和PCNA在大肠上皮性肿瘤中的表达

用免疫组化方法检测突变型Ｐ５３蛋白、Ｃ－ｅｒｂＢ－２癌基因蛋白和增殖细胞核抗原（ＰＣＮＡ）在６０例大肠腺癌、２９例腺瘤及３３例息肉石蜡切片中的表达情况。结果Ｐ５３在大肠癌与腺瘤中均过表达,阳性率分别为７０％和４８．２８％;而在息肉与正常粘膜中不表达。Ｐ５３的表达还与大肠癌的分化程度和Ｄｕｋｅ＇ｓ分期以及与腺瘤的大小、类型和不典型增生程度有关（Ｐ＜０．０５）。Ｃ－ｅｒｂＢ－２仅在大肠癌中表达,阳性率６５％。其表达与大肠癌的分化,淋巴结转移及Ｄｕｋｅ＇ｓ分期等均无关（Ｐ＞０．０５）。ＰＣＮＡ１００％表达,其所表示的细胞增殖指数与Ｐ５３的表达在大肠癌与腺瘤中均呈正相关（分别为ｒ＝０．６８８７,Ｐ＜０．０１及ｒ＝０．８６９６,Ｐ＜０．０１）。结果表明Ｐ５３的表达与大肠上皮性肿瘤的生物学行为有着非常密切的关系。检测Ｐ５３与ＰＣＮＡ的表达水平将对大肠癌的早期诊治以及分析大肠癌的增殖活性和恶性度等方面均有重要意义。Ｃ－ｅｒｂＢ－２是大肠癌的癌性标志,有可能作为鉴别诊断依据之一。     

血管内皮生长因子表达及微血管密度与头颈肿瘤发展和转移的关系

研究血管内皮细胞生因子(VBGV)的表达及微血管密度(MVD)与头颈肿瘤发展及转移的关系.应用免疫组织化学S-P法,检测32例头颈恶性肿瘤、20例头颈良性肿瘤、16例头颈部无瘤组织石蜡标本组织中的血管内皮细胞生长因子(VEGF)的表达、微血管密度(MVD).头颈恶性肿瘤组织VEGF的表达及MVD明显高于头颈良性肿瘤及头颈无瘤组织(P<0.05),转移组比较非转移组高(P<0.05).此外,在头颈肿瘤的发展及转移中VEGF的表达及MVD具有显著的正相关关系(r=0.398,<0.05).VEGF与头颈肿瘤血管生成有密切关系;VEGF的表达和MVD的增高对头颈肿瘤发展及转移有促进作用,其检测有可能作为头颈肿瘤预后的指标.     

FEZF1在结直肠癌组织和癌旁正常组织中的表达及临床意义

本文旨在探究FEZF1蛋白在结直肠癌组织和癌旁组织中的表达和其临床意义.通过免疫组化实验和Western Blot实验以及细胞实验,发现FEZF1在结直肠癌组织中低表达,并且其表达与肿瘤淋巴结转移(tumor node metastasis,TNM)分期具有显著相关性,在FEZF1低表达时,RKO细胞增殖和迁移能力提高,FEZF1高表达时RKO细胞增殖能力减弱.本研究证明了FEZF1是结直肠癌中的一个低表达蛋白,其表达与结直肠组织癌变的发生、发展相关,并且FEZF1会抑制结直肠癌细胞的增殖和迁移.     

Effects of soy isoflavone extracts on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized nude mice

In this study, we explored the effects of soy isoflavone extracts on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice. The ovariectomized athymic mice were implanted with MCF-7 cells. They were fed with low, moderate and high doses of soy isoflavone extracts, at dietary concentrations of 6.25, 12.5 and 25 g/kg, respectively. The expression of ki-67 was detected by immunohistochemistry. The pS ₂ expression in tumors was analyzed by real-time PCR. Estrogen level in the serum was measured by chemiluminescence enzyme immunoassay. Compared with the control group, dietary soy isoflavone extracts had a significant stimulatory effect on MCF-7 tumor growth in mice (P < 0.05). The ki-67 and pS ₂ mRNA expressions in tumors were significantly increased by 6.25 and 12.5 g/kg dose of soy isoflavone extracts (P < 0.05). And, estrogen level in serum of 6.25 and 12.5 g/kg dose groups was higher than that of control group (P > 0.05). In conclusion, in the tested dietary concentration range soy isoflavone extracts had a stimulatory effect on tumor growth. 6.25 and 12.5 g/kg doses of soy isoflavone extracts can increase the cell proliferation in tumors and induce estrogen-responsive pS2 expression. Supported by National Natural Science Foundation of China (Grant No. 30572133)     

Differentiation and adaptation epigenetic networks: Translational research in gastric carcinogenesis

There are several kinds of epigenetic networks in the human body including the cell differentiation epigenetic network(DiEN) and the host adaptation epigenetic network(AdEN).DiEN networks are static and cell/tissue-specific.AdEN networks are variable and dependent upon environmental factors.DiEN and AdEN alterations can respectively serve as biomarkers for different kinds of diseases.Cancer is a consequence of accumulated pathophysiological adaptations of tissue stem cells to exposure of environmental carcinogens.Cancer cells are de-differentiated cells that obtain the capacity of unrestricted proliferation,local invasion,and distant migration/metastasis.Both DiEN and AdEN changes can be observed in cancer tissues.Alterations of DNA methylation are the most stable epigenetic modifications and can be sensitively detected in a small cell population.These advantages make DNA methylation the optimal biomarkers for detection of initiated cells in precancerous lesions and metastasis stem cells in cancer tissues.It has been proven that p16 methylation can be used as a diagnostic biomarker to determine malignant potential of epithelium dysplasia in many organs including the stomach.In a large-scale validation study on the DNA methylome of gastric carcinomas(GC),the methylation status of more than 90 CpG islands has been analyzed by DHPLC.Furthermore,GFRA1 demethylation and methylation of SRF and ZNF382 are frequent events during gastric carcinogenesis and consistently correlate to GC metastasis and overall survival of GC patients from China,Japan,and Korea,respectively.In a population study,it has been demonstrated that gradual increasing of plasma miR-211 and other miRNA levels may be an early risk predictor for GC development.     

胃癌组织中环氧化酶-2和血管内皮生长因子-C、D、R3 mRNA表达的研究

目的:环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)-C、D及其受体3(R3)与肿瘤关系密切.研究COX-2和VEGF-C、D、R3在胃癌中的表达,探讨其在胃癌淋巴管生成和转移中的作用及其相关性.方法:采用RT-PCR方法,对22例胃癌及癌旁组织手术标本中COX-2和VEGF-C、D、R3mRNA的表达进行半定量研究.结果:胃癌组织中COX-2和VEGF-C、VEGF-R3mRNA表达均高于相应的癌旁非癌组织(P<0.05),其中COX-2和VEGF-C在淋巴结转移组中的表达均高于非淋巴结转移组(P<0.05),且COX-2和VEGF-C mRNA表达间存在明显相关性(P<0.05).结论:胃癌组织中有COX-2和VEGF-C、D、R3的高表达,而COX-2可能参与VEGF-C、D和/或R3淋巴管生成通路,其表达可能在胃癌淋巴管浸润和转移过程中发挥着重要作用.     

Assessment of alternated cooling and heating treatment by US combined CEUS in the VX2 rabbit liver tumor model

Inoperable liver tumors are often treated by thermal ablation that destroys the tumor in situ and spares the adjacent hepatic tissue.Thermal–physical treatment has many advantages,but treatment by freezing or heating alone has some limitations.By taking the advantages and disadvantages of cryosurgery and thermotherapy into consideration,a new thermal technique that combines cryosurgery and radio frequency ablation has been proposed,thereby overcoming the disadvantages of each treatment strategy and improving therapeutic outcomes.This new approach remains to be systematically studied in the liver;therefore,this study was performed to estimate survival after alternated cooling and heating ablation therapy in a VX2 rabbit liver tumor model.Sixteen days after VX2 carcinoma implantation into the rabbit liver,tumors were treated with alternated cooling and heating ablation therapy.Rabbits were monitored for 6 months after treatment and assessed with ultrasound(US)and computed tomography at 1,7,14,and 30 days posttreatment.Untreated tumor-bearing animals served as the control group.Our results show that alternate freezing and heating ablation therapy resulted in a good recovery of VX2 rabbits.Compared with the control group,treated rabbits lived significantly longer(P\0.05),with 70%of treated animals surviving to 196 days posttreatment without metastasis or recurrence,while none of the controls did so.There was no local recurrence in the treatment group.All rabbits in the control group developed metastasis,while metastasis was only observed in 30% of treated rabbits.These results suggest that alternate cooling and heating ablation therapy can prolong the survival time of rabbits with VX2 liver tumors and is an effective method for tumor therapy.Furthermore,we also showed in this model that contrast enhanced US is a valid follow-up approach to assess treatment effectiveness.     

AgNOR和p53在大肠癌中的表达

目的研究AgNOR和p53在大肠癌中的表达及其与大肠癌发生、发展及预后的关系.方法选用大肠癌组织标本80例及相应的癌旁组织标本40例,采用AgNOR染色技术和免疫组织化学法检测大肠癌组织及癌旁组织中AgNOR计数和p53的表达.结果大肠癌中AgNOR计数显著升高,细胞核内AgNOR计数、颗粒分布及形态特点与大肠癌的分化程度、淋巴结转移有相关性(P<0.05);p53在大肠癌组的阳性表达率为66.3%,在癌旁组的阳性表达率为20.8%.两者之间存在显著性差异(P<0.01);大肠癌组织中p53的阳性表达与大肠癌的分化程度、淋巴结转移有相关性(P<0.05),而与大肠癌的发病年龄、性别无关(P>0.05).结论 p53的突变在大肠癌的形成和发展中起了促进作用,AgNOR测定对大肠癌的病理学分级有一定的价值,同时说明AgNOR和p53有可能作为大肠癌发生、发展及预后的肿瘤标志.     

生殖细胞核因子及其相关因子在恶性生殖细胞肿瘤中的表达

为研究生殖细胞核因子（GCNF）及Oct-4在恶性生殖细胞肿瘤中的表达,揭示GCNF及Oct-4在恶性生殖细胞肿瘤中关系。运用免疫组化SP法分别检测41例男女生殖系统恶性肿瘤及8例无瘤变卵巢组织及10例无瘤变睾丸组织中GCNF及Oct-4的表达。结果显示GCNF在所有的恶性生殖细胞肿瘤及无瘤变的睾丸组织均呈阳性表达,定位于肿瘤细胞的细胞核,Oct-4在未成熟畸胎瘤,无性细胞瘤及精原细胞瘤呈阳性表达,定位于肿瘤细胞的细胞核,在其他类别的恶性生殖细胞肿瘤及无瘤变卵巢组织及睾丸组织中不表达。由此可知,GCNF和Oct-4在恶性生殖细胞肿瘤中的表达呈负相关,二者的表达强度可能与肿瘤细胞的分化状态有关。     

RhoC和MMP-9蛋白在结直肠癌中的表达及意义

探讨RhoC和基质金属蛋白酶-9（MMP-9）蛋白在结直肠癌发生发展中的作用。选取新鲜结直肠癌标本作为实验组,正常新鲜结肠粘膜组织作为对照组,应用流式细胞术分别检测RhoC和MMP-9的表达,检测其在不同临床病理特征之间的关系。结果表明,RhoC和MMP-9在结直肠癌组织中高表达（P〈0．05）,且其表达均与Dukes分期、浸润深度及炎细胞浸润相关（P〈0．05）,MMP-9的表达与结直肠癌的淋巴结转移密切相关（P〈0．05）,Rhoc和MMP-9在结直肠癌中的表达呈正相关（r=0．3430,P=0．0420）。流式细胞术联合检测RhoC和MMP-9蛋白的表达有望成为判断预后的重要指标。     

环氧合酶-2在大肠癌组织中的表达及临床意义的研究

目的探讨COX-2蛋白在大肠癌中的表达与肿瘤发生发展和转移的关系.方法应用免疫组化SP法检测COX-2蛋白在66例大肠癌及22例正常大肠组织的表达情况.结果COX-2蛋白在66例大肠癌组织中高表达(56/66),阳性表达率84.8%,与正常大肠组织相比差异有显著性(P<0.01);COX-2蛋白的表达与肿瘤组织的浸润深度显著相关(P<0.05);与Dukes分期呈正相关(P<0.05);淋巴结有转移组与无转移组差异有显著性(P<0.05).结论COX-2在大肠癌的发生、发展及浸润、转移过程中发挥着重要作用,可望成为预测大肠癌恶性潜能的临床指标之一.