姜黄素对人胃癌细胞SGC-7901的影响

目的 探讨姜黄素对人胃癌细胞SGC-7901的影响.方法 人胃癌细胞SGC-7901接受不同浓度姜黄素处理,然后采用MTT法测定人胃癌细胞SGC-7901的增殖,Boyden chamber侵袭小室测定细胞侵袭能力,划痕实验测定细胞迁移能力.结果 姜黄素能够抑制人胃癌细胞SGC-7901增殖,且作用与药物浓度有关(P＜0.05),浓度越大,抑制能力越强;姜黄素能够抑制人胃癌细胞SGC-7901侵袭、迁移,且作用与药物浓度有关(P＜0.05),浓度越大,抑制能力越强.结论 姜黄素能够抑制人胃癌细胞SGC-7901的增殖、侵袭、迁移,且这种作用具有剂量依赖性.     

NHE1反义基因磁性纳米微粒对SGC-7901胃癌细胞增殖和凋亡的影响

目的:探讨NHE1反义基因磁性纳米微粒对SGC-7901胃癌细胞株增殖和凋亡的影响,探索胃癌基因治疗的新方法。方法:构建NHE1反义基因真核表达载体和NHE1反义基因磁性纳米微粒,将NHE1反义基因转染至SGC-7901胃癌细胞中,比较观察细胞转染前后生长曲线、细胞周期和细胞凋亡率的变化。结果:氧化铁磁性纳米颗粒成功地将NHE1反义基因转染至SGC-7901胃癌细胞中。NHE1反义基因能使SGC-7901胃癌细胞生长速度减慢、体外生长增殖能力降低,转染NHE1反义重组质粒的SGC-7901胃癌细胞增殖指数为34.73%,低于SGC-7901细胞的38.95%;NHE1反义基因使SGC-7901胃癌细胞凋亡率增加,转染NHE1反义重组质粒的SGC-7901胃癌细胞凋亡率为11.75%,显著高于SGC-7901胃癌细胞凋亡率(3.85%,P<0.01)。结论:NHE1反义基因磁性纳米微粒能抑制SGC-7901胃癌细胞增殖,诱导细胞凋亡,具有良好的治疗效果,有一定的临床应用前景。     

康艾注射液对胃癌细胞SGC-7901的抑制作用

目的探讨康艾注射液对胃癌细胞SGC-7901的抑制作用。方法胃癌细胞SGC-7901接受不同浓度康艾注射液,然后采用MTT法测定各组胃癌细胞SGC-7901的增殖情况,Boyden chamber侵袭小室测定各组胃癌细胞SGC-7901侵袭能力,划痕实验测定各组胃癌细胞SGC-7901迁移能力。结果康艾注射液对胃癌细胞SGC-7901增殖的抑制与药物浓度有关(P<0.05),浓度越大,抑制能力越强;康艾注射液对胃癌细胞SGC-7901侵袭、迁移的抑制与药物浓度有关(P<0.05),浓度越大,抑制能力越强。结论康艾注射液对胃癌细胞SGC-7901的增殖、侵袭、迁移均有抑制作用,且具有剂量依赖性。     

去甲斑蝥素对人胃癌SGC-7901细胞增殖的影响及其机制探讨

目的:探讨去甲斑蝥素(norcantharidin,NCTD) 对人胃癌SGC-7901细胞系增殖的影响及其机制.方法:实验分NCTD 组和对照组,分别应用MTT、流式细胞术、光学显微镜和电子显微镜检测 NCTD 对体外培养的胃癌SGC-7901细胞的杀伤抑制率、细胞周期、凋亡和细胞形态学改变.结果: NCTD对SGC-7901 细胞增殖有抑制作用,随浓度升高、时间延长作用增强,呈剂量- 时间依赖关系.在实验组,流式细胞仪示SGC-7901 细胞的G2 M 期细胞明显增多,S 期细胞减少,凋亡率上升;光镜和电子显微镜下出现细胞固缩,胞膜突出,核碎裂和凋亡小体.结论: NCTD 能抑制人胃癌SGC-7901细胞的生长;其机制可能与其抑制SGC-7901 细胞增殖、干扰增殖周期、抑制DNA 合成代谢、诱导细胞凋亡有关.     

NHE1反义基因磁性纳米微粒对SGC-7901胃癌细胞增殖和凋亡的影响

目的：探讨NHE1反义基因磁性纳米微粒对SGC-7901胃癌细胞株增殖和凋亡的影响，探索胃癌基因治疗的新方法。方法：构建NHE1反义基因真核表达载体和NHE1反义基因磁性纳米微粒，将NHE1反义基因转染至SGC-7901胃癌细胞中，比较观察细胞转染前后生长曲线、细胞周期和细胞凋亡率的变化。结果：氧化铁磁性纳米颗粒成功地将NHE1反义基因转染至SGC-7901胃癌细胞中。NHE1反义基因能使SGC-7901胃癌细胞生长速度减慢、体外生长增殖能力降低，转染NHE1反义重组质粒的SGC-7901胃癌细胞增殖指数为34．73％，低于SGC-7901细胞的38．95％；NHE1反义基因使SGC-7901胃癌细胞凋亡率增加，转染NHE1反义重组质粒的SGC-7901胃癌细胞凋亡率为11．75％，显著高于SGC-7901胃癌细胞凋亡率（3．85％，P〈0．01）。结论：NHEl反义基因磁性纳米微粒能抑制SGC-7901胃癌细胞增殖，诱导细胞凋亡。具有良好的治疗效果，有一定的临床应用前景。     

去甲斑蝥素诱导人胃癌SGC-7901细胞凋亡的机制研究

[目的]探讨去甲斑蝥素对人胃癌SGC-7901细胞抑制和诱导凋亡作用.[方法]采用不同浓度的去甲斑蝥素(noncantharidin,NCTD)作用于胃癌SGC-7901细胞,在扫描电镜下观察其形态特点,采用流式细胞术测定经NCTD作用后的细胞生长周期及凋亡率,Western-blot 检测Bcl-2、Mcl-1、Bax的表达.[结果]扫描电镜下可见,SGC-7901细胞出现凋亡形态学改变.经去甲斑蝥素处理SGC-7901细胞后,实验组G2/M细胞明显多于对照组(P＜0.05).10μg//m1和20μg/ml浓度去甲斑蝥素均能诱导胃癌SGC-7901细胞凋亡(P＜0.05),其抑制率与NCTD浓度及作用时间相关.Western-blot检测Bcl-2、Mcl-1蛋白表达减少,Bax蛋白表达增加,呈明显的剂量关系.[结论]去甲斑蝥素对人胃癌SGC-7901细胞有抑制作用,可能与其阻滞细胞周期诱导细胞凋亡有关.     

Src激酶抑制剂PP2对人胃癌细胞生物学行为的影响

目的:探讨Src激酶抑制剂PP2对人胃癌SGC-7901细胞生长、迁移、侵袭和诱导血管形成等生物学行为的影响.方法:通过Western印迹法检测PP2作用对SGC-7901细胞中Src激酶活化的影响;分别采用MTT法、划痕实验、Transwell小室法和体外诱导血管形成分析实验观察PP2对SGC-7901细胞生长、迁移、基质侵袭和诱导血管形成等生物学行为的影响.结果:MTT法检测结果提示,15 μmol/L PP2作用人胃癌SGC-7901细胞12 h时能明显抑制细胞的增殖;5和10 μmol/L PP2均能抑制SGC-7901细胞的迁移、侵袭和诱导血管的形成,且其抑制能力随PP2浓度的增加而逐渐增强.结论:Src激酶抑制剂PP2具有抑制人胃癌SGC-7901细胞生长、迁移、侵袭和诱导血管形成的能力,可能对胃癌具有一定的治疗效果.     

γ-生育三烯酚对人胃癌 SGC-7901细胞的抑制作用及机制

目的 探讨γ -生育三烯酚(γ -tocotrienol)对人胃癌细胞SGC-7901抑制作用.方法 采用离体细胞培养技术,利用细胞生长曲线,单细胞凝胶电泳、琼脂糖凝胶电泳、透射电镜技术等方法,观察 γ-生育三烯酚对SGC-7901细胞生长抑制及其肿瘤细胞的损伤作用.结果 γ -生育三烯酚可明显抑制SGC-7901细胞增殖,抑制作用随作用浓度增加、作用时间延长而增强;并能引起人胃癌细胞株SGC-7901细胞DNA 分子的损伤以及细胞超微结构变化,如线粒体损伤和形成凋亡小体,且与γ-生育三烯酚作用的浓度存在一定的相关性.结论 γ -生育三烯酚对SGC-7901细胞生长有明显抑制作用,其抑制机制与参与DNA损伤、诱导细胞凋亡有关.     

SDZ对人胃癌SGC-7901细胞的影响

[目的]观察SDZ体外对人胃癌SGC-7901细胞的影响。[方法]培养人胃癌SGC-7901细胞,加入不同浓度的SDZ,作用24h、48h、72h,用MTT法计算细胞生长抑制率,描绘细胞生长曲线,荧光染色和电镜检测并观察细胞凋亡情况。[结果]SDZ体外对人胃癌SGC-7901细胞的生长抑制率随作用浓度和作用时间的增加而增大。1000μg/ml、200μg/ml、40μg/ml、8μg/ml、1.6μg/mlSDZ对人胃癌SGC-7901细胞作用24h,细胞抑制率分别为38%、35%、33%、29%、20%。[结论]SDZ体外对人胃癌SGC-7901细胞有生长抑制作用,呈剂量依赖性和时间依赖性,与细胞生长抑制率呈正相关,能引起细胞凋亡。     

氧化苦参碱对人胃癌SGC-7901细胞株的杀伤作用

目的探讨氧化苦参碱（OM）对于人胃癌SGC-7901细胞株的杀伤作用。方法采用四甲基偶氮唑蓝（MTT）比色法检测OM对人胃癌SGC-7901细胞的杀伤作用。结果证实OM在浓度〉2gm/mL时对人胃癌SGC-7901细胞具有杀伤作用，而当浓度〈1mg/mL则无明显的细胞毒性作用。结论OM对人胃癌SGC-7901细胞株具有剂量依赖性杀伤作用。     

破坏血管和肿瘤细胞毒性药物联合应用治疗胃癌的实验研究

 本研究联合应用血管破坏药物，加强肿瘤细胞毒性药物抗肿瘤疗效。利用局部注射途径，采用乳剂型制剂，减少药物副作用，尽可能使药物长久地留置于癌肿周围，为临床治疗胃癌提供实验依据。结果表明：中药乳剂性质稳定，对免耳血管有明显的破坏作用，导致出血性改变，对CAM血管生长有明显的抑制效应，联合应用中药乳剂和丝裂霉素C能提高抗肿瘤疗效。     

Tumor regression mechanisms by IL-13 receptor-targeted cancer therapy involve apoptotic pathways

IL-13 cytotoxin, composed of IL-13 and a truncated form of Pseudomonas exotoxin, targets IL-13R-overexpressing tumor cell lines in vitro and in vivo. To reveal the molecular mechanism of IL-13 cytotoxin-induced cell death in vivo, we demonstrate activation of apoptotic pathways in 2 s.c. growing human SCCHN tumor models in immunodeficient mice after i.t. administration of IL-13 cytotoxin. Treatment of HN12 tumor bearing mice with i.p. or i.t. administration of IL-13 cytotoxin mediated marked regression of established tumors with complete remission. Interestingly, after a single i.t. administration, IL-13 cytotoxin disappeared within 6 hr but accumulation of caspase-3, -8 and -9 and cleavage of procaspase-3 and PARP continued within the tumors for a prolonged period. We further demonstrate that IL-13 cytotoxin also utilizes an alternate pathway of cell death via the release of cytochrome c from mitochondria to the cytosol. Our results indicate that IL-13 cytotoxin induces 2 major pathways of apoptosis, which may play a role in tumor regression. In addition, apoptotic molecules may serve as surrogate molecular markers of tumor response to IL-13R-directed cytotoxin therapy.     

Phenotypic heterogeneity of leukemias associated with Friend MuLV infection: studies on T-cell lymphomas and null cell leukemias in euthymic and thymus-deficient mice

The development of leukemia/lymphoma in euthymic and congenitally thymus-deficient (nude) mice infected with Friend murine leukemia virus (Friend MuLV) was investigated; both groups developed fatal leukemias within 2-4 months post-infection but the gross and micropathology of lymphoid organs, coupled with cell-surface marker studies indicated the development of two distinct forms of disease. In euthymic mice one group developed lymphosarcomas manifested by thymoma, hepatosplenomegaly and lymphadenopathy whereas the second group developed splenic leukemias manifested only by hepatosplenomegaly. Analysis of surface markers on spleen cells from mice experiencing lymphosarcomas indicated that the majority of cells were positive for Thy 1.2, Moloney cell surface antigen (MCSA), and viral-coded gp70 and p30 antigens but negative for surface immunoglobulin (sIg). Euthymic mice experiencing splenic leukemias yielded spleen cells negative for Thy 1.2, sIg, and MCSA but positive for gp70 and p30. Nude mice uniformly developed splenic leukemias, spleen cells from which were Thy 1.2, MCSA, gp70 and p30 negative, although the proportion of sIg positive cells was higher than that observed in euthymic mice experiencing splenic leukemias. No correlation between the development of lymphosarcoma vs splenic leukemia and a pattern of ecotropic and/or xenotropic MuLV expression was observed. While ecotropic MuLV expression was equivalent in both euthymic and athymic mice, euthymic mice expressed approx. 10-fold higher levels of xenotropic MuLV than nude mice, however. Collectively the data suggest that infection of mice with Friend MuLV results in the development of two possible forms of disease, lymphosarcoma involving T cells vs splenic leukemia involving B and/or null cells.     

Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecularly targeted anti-cancer agents being used to attack malignancy in a rational manner. A large body of preclinical data indicates that FTase inhibitors block cancer cell proliferation through both cytostatic and cytotoxic effects. Interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they may target unique aspects of cancer cell pathophysiology. The development of FTase inhibitors was predicated on the discovery that the Ras oncoproteins must be post-translationally modified to transform cells. However, recent work indicates that the anti-neoplastic effects of FTase inhibitors depend on altering the post-translational modifications of non-Ras proteins as well. In particular, a critical target protein that responds to FTase inhibition by blocking tumor cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In this review, we survey the biological foundations for the clinical development of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.     

Targeting tumor vasculature with homing peptides from phage display

Tumor vasculature expresses a number of molecular markers at much lower levels than those seen in the blood vessels of normal tissues, and in some cases, such markers are undetectable. The presence of these markers relates to angiogenesis; the same markers are shared by all blood vessels undergoing angiogenesis. The endothelial cells, pericytes and smooth muscle cells, and the vascular extracellular matrix in angiogenic vessels can each express such markers. Molecularly, they represent vascular growth factor receptors, cell adhesion proteins and their receptors. Screening of phage display libraries for peptides that home to tumor vasculature when injected into mice has recently provided a new tool for analyzing the distinguishing features of tumor vasculature. Tumor-homing peptides isolated in this manner, as well as an antibody against a form of fibronectin expressed in tumor blood vessels, have been found to serve as targeting devices to concentrate drugs and other therapeutic materials to tumors in in vivo models. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.     

Identification of EBV transforming genes by recombinant EBV technology

Epstein-Barr virus (EBV) is able to infect primary B-lymphocytes but usually does not proceed to replicate more virions. Instead, EBV persists as an incomplete virus and expresses 12 gene products that transform the growth of these cells into continuously proliferating lymphoblastoid cell lines. Because EBV is associated with several human malignancies, there is intense interest in delineating the molecular functions of these EBV gene products in transformation. This review focuses on the recombinant EBV technologies that have been developed to introduce specific mutations into EBV and test the functions of these EBV genes in primary B-lymphocyte growth transformation.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

New aspects of integrin signaling in cancer

Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behavior, including motility and invasiveness, cell growth, and cell survival. Engagement of integrins with extracellular matrix (ECM) proteins can activate members of the Rho-family of small GTPases; conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands. These events impinge on the control of cell motility, and ultimately on invasive and metastatic behavior. Integrin engagement with ECM also has important effects on cell survival, particularly for cells of epithelial origin. In some cases, specific integrins have selective effects on the efficiency of signal transduction in cell survival pathways.     

Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.     

ABCG2在肺癌中表达的定量研究

目的 观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义.方法 常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度.结果 ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜.在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P＜0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零.癌周肺组织表达的PU值高于各型肺癌(P＜0.05).ABCG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P＞0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P＞0.05),与肺癌分化程度有关(P＜0.001).分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P＞0.05).结论 ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一.