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埃兹蛋白、上皮型钙黏着蛋白、桩蛋白、整合素β1蛋白在皮肤鳞状细胞癌中的表达
目的 探讨埃兹蛋白(ezrin)、上皮型钙黏着蛋白(E-cadherin)、桩蛋白(paxillin)和整合素β1(INTβ1)在皮肤鳞状细胞癌(SCC)中的表达及意义.方法 应用免疫组化法对30例SCC患者及10例正常对照者的ezrin、E-cadherin、paxillin和INTβ1表达进行检测.结果 正常人表皮角质形成细胞上均表达ezrin和E-cadherin(10/10),表达率显著高于SCC肿瘤细胞[56.67%(17/30)和13.33%(4/30),x2分别为6.42和24.76,P值均<0.05];正常人表皮角质形成细胞上paxillin和INTβ1的表达率为0和10.00%(1/10),均显著低于SCC肿瘤细胞[70.00%(21/30)和66.67%(20/30),x2分别为14.74和9.66,P值分别< 0.01和0.05].SCC肿瘤细胞ezrin和E-cadherin的表达呈显著正相关(r=0.52,P< 0.01),paxillin和E-cadherin、INTβ1与E-cadherin的表达均呈显著负相关(r值分别为-0.56和-0.52,P值均<0.01);ezrin与paxillin、Ezrin与INTβ1、paxillin与INTβ1的表达无相关性(r值分别为0.5、0.24和0,P值均>0.05).结论 E-cadherin低表达、paxillin和INTβ1高表达可能共同促进肿瘤细胞的侵袭和转移;INTβ1与E-cadherin在SCC转移中可能起到拮抗作用.
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融合蛋白表达载体MK-EGFP的构建及其在不同肿瘤细胞中的定位
MK(Midkine)是一种肝素结合性生长因子,初发现与细胞生长、迁移和存活有关,随后的研究发现它在多种人源恶性肿瘤中高表达[1-2].
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消化道肿瘤细胞Gastrin/CCK自分泌调节环路的研究进展
胃泌素(Gastrin)和胆囊收缩素(Cholecystokinin,CCK)是古老而具代表性的同族消化道激素,近20年来,它们作为单纯消化道激素的概念发生了巨大变化,Gastrin/CCK对消化道肿瘤的调控作用已成为人们关注的焦点[1,2].大多数消化道肿瘤细胞能合成和分泌Gastrin/CCK、并表达相应受体,其分泌的Gastrin/CCK通过自身的受体后途径发挥对肿瘤的调节作用,此即消化道肿瘤细胞的Gastrin/CCK自分泌调节环路(au-tocrine loop),这可能是消化道肿瘤细胞重要的生物学特性和自主性调控机制之一[3,4].
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结直肠癌循环肿瘤细胞临床应用的研究进展
结直肠癌是常见的恶性肿瘤之一,发病率仅次于肺癌和乳腺癌,死亡率位居第四,大量患者死于术后转移和复发.循环肿瘤细胞在结直肠癌的血行转移中具有极其重要的作用.近年临床研究显示循环肿瘤细胞(circulating tumer cell,CTC)与结直肠癌临床分期有关,有助于结直肠癌的早期诊断、预后评估以及个体化治疗方案的制定.本文综述近年来有关结直肠癌循环肿瘤细胞的临床研究进展.
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精氨酸甲基转移酶在癌症发病机制中的作用
Tumor development of human takes multiple steps over a long period of time.The multiple steps with DNA mutations on genes is important for maintaining genome stability.Cell cycle and differentiation and epigenetic changes give rise to funor stem cells,which produce the mass of heterogeneous tumor cells.The cancer stem cell theory indicates that cancer cells are heterogeneous with a hierarchal structure,and only the cancer stem cells have the ability of self-renewal and to initiate tumorigenesis in a series of transplantation in xenograft models[1].
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微量循环肿瘤细胞检测技术的研究进展
肿瘤的发生发展是一个多基因参与,多因素、多步骤的复杂的生物学过程.肿瘤刚发生时多为器官局限性疾病,绝大多数肿瘤组织通过其脱落细胞进入血液循环,进而侵袭其它脏器进行远处转移.早于1869年,Ashworth在一例肿瘤死亡患者外周血中发现了类似肿瘤细胞,并首次提出循环肿瘤细胞(Circulating Tumor Cells, CTCs)的概念[1].CTCs定义是指自发的或者因诊疗操作由实体瘤或者转移灶释放进入外周血中进行循环的肿瘤细胞[2].CTCs的检测可能有效地应用于体外早期诊断、化疗药物的快速评估、肿瘤复发的监测以及抗肿瘤新药物的开发等.
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泌尿系统肿瘤循环肿瘤细胞的检测
恶性肿瘤患者往往死于全身转移,如果能在转移灶出现之前进行预测,就可以采取更加积极主动的治疗.恶性肿瘤的全身转移是癌细胞自原发灶脱落进入血循环并在其他部位定植的过程,循环肿瘤细胞(circulating tumor cells,CTCs)的出现是恶性肿瘤全身转移过程中重要的一步.早在1869年,Ashworth[1]就报道在1例癌症死亡患者的外周血中发现了类似肿瘤的细胞,并首次提出CTCs的概念.检出CTCs并不意味着有远处转移,但以往对恶性肿瘤的研究表明出现CTCs往往代表不良预后.
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儿童后颅凹室管膜瘤(附243例分析)
室管膜瘤是儿童期比较常见的颅内肿瘤,多数位于后颅凹.现将我院1958~1981年收治,并经病理证实的儿童后颅凹室管膜瘤(包括室管膜母细胞瘤)243例的诊治经验介绍如下.临床资料一、性别及年龄本组男性145例(59.7%),女性98例.年龄分布:4个月~3岁32例,4~7岁76例,8~12岁99例,13~15岁36例.年龄:小者为4个月,平均就诊年龄为8.1岁.
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特异性脐血DC疫苗对Beige裸鼠人结肠癌动物模型荷瘤免疫治疗作用的实验研究
背景:肿瘤免疫治疗目前在临床治疗中已广泛开展,但是临床上经过反复输注后,由于机体内肿瘤免疫抑制因素的增多出现了治疗效果下降的情况,严重影响了长期治疗效果,本实验通过构建二次成瘤模型尽可能的模拟人体的肿瘤发生及术后复发转移的肿瘤微环境,通过采用外源性脐血特异性Dc疫苗,起到改善体内免疫细胞功能,减少体内免疫抑制因素,从而达到改善肿瘤患者体内免疫微环境,发挥增强肿瘤免疫治疗效果的临床治疗目的。目的:通过成功构建SCID/Beige裸鼠人结肠癌动物模型,研究脐血来源特异性Dc疫苗对人源化免疫重建荷瘤裸鼠成瘤的免疫抑制作用。方法:分别选取健康志愿者外周血及正常分娩足月产孕妇脐带血,利用密度梯度离心法贴壁培养不同来源Dc细胞制备负载人结肠腺癌SW-1116抗原的特异性抗原提呈细胞,促其成熟后收获;选用健康雄性SCID/Beige裸鼠构建动物模型,将人SW-1116细胞接种于裸鼠腋窝皮下,观察并确定成瘤。空白对照组无任何预先处理,实验组、对照组及阴性对照组确定成瘤后自鼠尾静脉注入健康志愿者外周血PBMC行人免疫细胞微环境重建,在行二次荷瘤前24 h实验组给予脐血Dc疫苗尾静脉注射,实验对照组给予健康志愿者Dc疫苗尾静脉注射,阴性对照组给予健康志愿者无负载抗原的Dc疫苗尾静脉注射;经上述处理后在荷瘤裸鼠对侧腋窝皮下接种人SW-1116细胞,分别观察不同荷瘤组裸鼠二次荷瘤后的一般生活状态、成瘤时间、成瘤大小及瘤重。结果:空白组裸鼠双侧肿瘤生长快,裸鼠短时间内出现肿瘤破溃,部分出现活动差及死亡;经免疫预防处理后荷瘤裸鼠一般生活情况良好,肿瘤生长缓慢,肿瘤体积较小,无破溃、坏死及裸鼠死亡;脐血来源Dc细胞能够负载人结肠癌细胞株SW-1116抗原,并进一步活化成熟发挥其专职抗原提成能力;脐血Dc实验组裸鼠瘤重及瘤终体积平均值明显小于对照组及阴性对照组,比较统计学差异显著。结论:脐血特异性DC疫苗能够改善外周血免疫细胞的免疫功能,促进增强其自身肿瘤免疫杀伤能力,对瘤细胞生长有明显抑制,延缓其肿瘤进展及程度,有积极的肿瘤免疫治疗作用。
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循环肿瘤细胞的检测方法
在原发上皮肿瘤形成和生长的早期,肿瘤细胞便可以通过血流播散到远处器官.这些循环肿瘤细胞(circulating tumor cells,CTCs)可以通过不同技术进行富集和检测,其分析被认为是对癌症患者的实时“液体活检”.这种活检能对CTCs特异性亚群进行表征,且有可能为癌症的检测和控制带来革命性的转变.本篇作者将着重讨论当前用于CTCs富集和检测的策略.
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新兴的肺癌肿瘤标志物——循环肿瘤细胞
近来,循环肿瘤细胞(circulating tumor cells,CTCs)作为潜在的预后标志物和预测转移进展的可靠手段在肿瘤研究中引起了密切关注.早在19世纪就有多名科学家和医生对CTCs进行了描述,其存在作为发生远端转移的必要条件并非新的概念.然而直到近,能够准确识别癌症患者血液中CTCs的生物技术才得到广泛运用.例如,基于免疫磁性技术的CellSearch (Veridex,LLC),由包覆抗上皮细胞黏附分子(epithelial cell adhesion molecule,EpCAM)抗体的磁性纳米颗粒组成,是目前CTCs的佳检测系统之一.由于通过CellSearch鉴定的CTCs在开展新的化学治疗前对乳腺、前列腺和结直肠肿瘤具有一定的预测价值,美国食品药物管理局批准了这类方法在上述疾病中的应用[1].
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非小细胞肺癌中的循环肿瘤细胞
肺癌是世界上致命的癌症类型.仅仅在美国,每年就有超过225000人被确诊为肺癌,2012年预计死于肺癌的患者大约有16万[1].与癌胚抗原(carcinoembryonic antigen,CEA)在结肠癌以及前列腺特异抗原(prostate specific antigen,PSA)在前列腺癌中的作用不同,在肺癌患者诊治过程中,肿瘤标志物的应用并不广泛.肺癌的诊断依赖于影像学检查,而不是体液中的肿瘤标志物.然而在近的研究中,循环肿瘤细胞(circulating tumor cells,CTCs)的潜在价值被发现.基于CTCs的分析已经被视作“液相活组织检查”,它将有助于我们对恶性肿瘤进行定性和定量的分析[2].
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肺癌循环肿瘤源性生物标志物
美国国立卫生研究院生物标志物定义工作组将生物标志物定义为“一种具有能客观测量同时可用于评价一般生物过程、发病过程或医疗干预相关药物反应的指示物”[1].大量正在进行的肺癌相关研究致力于探讨用于早期诊断和高风险预测的气道上皮细胞、痰液、呼气、尿液和血液中的生物标志物.在此,着重评述肺癌的循环生物标志物,尤其是循环肿瘤细胞(circulating tumor cells,CTCs)与循环核酸(circulating nucleic acids,CNAs).
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循环肿瘤细胞的生物学和临床意义
循环肿瘤细胞(circulating tumor cells,CTCs)评估为探索肿瘤生物学提供了一种新的方法,CTCs也有可能作为有临床意义的生物标志物.长期以来,人们一直在猜测CTCs的存在以及它们在转移中的作用.近年来,可靠分离CTCs技术的出现,使这个领域重新获得关注.CTCs多常见于恶性肿瘤患者的血液中,在健康志愿者和良性疾病患者的血液中比较罕见[1].随着CTC分离技术的发展,可以在分子水平研究CTCs,有助于更好地了解转移生物学;CTCs可作为一种微创“液体活检”在患者的治疗过程中进行纵向监测.特别是这种方法还可用于描述肿瘤进展,评估药物研发的药效学生物标志物.以往连续对肺癌患者进行活检非常困难,因而了解肿瘤耐药机制是很有挑战性的课题,CTCs亦有助于揭示此机制.
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循环肿瘤细胞在非小细胞肺癌中的临床应用:我们达到目标了吗?
早在140年前,人们就在患者循环系统中发现了与患者原发肿瘤细胞形态学相似的肿瘤细胞[1].循环系统中的这些细胞很可能是患者原发肿瘤中脱落的,这个观点随着细胞遗传学技术的进步而得到了证实,表明这些循环细胞同样携带了原发肿瘤中检出的基因突变[2].然而直到近,这些循环肿瘤细胞(circulating tumor cells,CTCs)才开始被作为癌症患者诊断或预后的潜在标志物进行研究.由于CTCs数量非常稀少,研究进展较慢.此外,起源于原发性肿瘤或转移性播散的这些肿瘤细胞可能是具有较高异质性.过去十年中CTC分离新技术的发展使得CTCs受到大量关注,但这些方法的变化性以及在不同实验室中重现性的缺乏使数据解释变得困难[3].迄今为止,被认为能够在临床研究中提供可靠和可再现的CTC计数的唯一经验证的检测方法是CellSearch系统(Veridex,Raritan,NJ).由于CTCs在这些适应症中表现出的预后意义,以及治疗中CTC数量改变被证明是预测性生物标志物,这项技术获得了美国食品和药物管理局的批准,作为转移性乳腺癌、结肠癌和前列腺癌患者检测的辅助手段.
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In this experiment, Hca-F or L615 elemene combo-TCV (H-TCV and L-TCV), H-TCV lysates, corynebacterium parvum (CP) were used to immunize 615 and Balb/c inbred mice, and their splenic DCs were prepared and pulsed in vitro with tumor cell lysates (H or L) and TCV lysates (TH or TL). The capacities of DCs to stimulate the proliferation of syngeneic nonadherent spleenic cells were tested with MTT assay. The results showed that the splenic DCs from normal mice in vitro pulsed with TH or TL could induced syngeneic noradherent splenic cells to proliferate (P<0.01), while the H or L pulsed DCs could not. The splenic DCs from H-TCV or L-TCV or TH immunized mice re-pulsed in vitro with TH or TL exhibited stronger stimulating effects than the DCs from normal mice pulsed in vitro for the firth time pulsed with TH or TL (P<0.01 or P<0.05); The capacities of DCs to induce proliferation of syngeneic nonadherent splenic cells could be further enhanced by CP immunization, especially when were pulsed with TH (P<0.01). Normal inbred 615 mice were transferred with DCs pulsed with lysates of elemene TCV (TDCs) or pulsed with lysates of Hca-F tumor cells (HDCs) on day 7 before challenged with lethal dose of live Hca-F cells, significant adoptive immunoprotective effects were seen, with 61.6% tumor inhibition rate and 25% survival in TDC adoptive transfer group. This study indicated that DCs might play a role in the mechanisms of active immunization and pulsing DCs with lysate of elemene combo TCV and isolating DCs from elemene combo TCV immunized mice were useful methods for DCs vaccine preparation.
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In this study, immunotoxin (IT) was prepared by conjugating BAC5 and CT with SPDP. The effects of IT on NPC and its mechanisms were explored using double labeled with radioactive nuclides, immunography and electron microscope technique in vivo and in vitro. The specific concentration of BAC5 in the tumor area showed. The radioactivity rate of tumor/nontumor (T/NT) was up to 10.26. IT had cytotoxic effects both on the cultured CNE-2 cell line and tumor multicell spheroides. In vivo, the preliminary result indicated that IT also had a inhibitory action on the nude mice models bearing human NPC (Reported in another article). Under electron microscope, the necrosis and apoptosis of tumor cells were found. The membranes of most tumor cells were found intacted not or corrosined, some of them had the character of apoptosis, including reduce of tumor cells membrane villi, condensation of cytoplasm and pyknosis or cleavage of nuclear. There were many of apoptosis bodies, which were occasionally phagocytosed by tumor cells. The infiltration of immunocytoes in tumor tissue could be seen. The results indicated that BAC5 can specifically combine with NPC cells and BAC5-CT has the inhibitory effect on NPC in vitro and in vivo, mechanism of which may be related to the effects that ‘warhead' CT dissolute the membrane of tumor cells directly, or/and IT promote the infiltration of immunocytoes so as to induce the apoptosis of tumor cell.
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TGFβ and Hypoxia Drive Breast Cancer Bone Metastases through Parallel Signaling Pathways in Tumor Cells and the Bone Microenvironment
Breast cancers frequently metastasize to bone, a site of hypoxia and high concentrations of active TGFβ. Skeletal metastases involve interactions between tumor and bone cells driven by locally secreted proteins, many of which are increased by hypoxia and TGFβ.
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Potential Significance of glioma Stem Cells in angiogenesis and immunopharmacological Therapeutics: Hypothesis and Evidences
Recent studies on cancer stem cells (CSCs), a special subpopulation of tumor cells, promote our understanding of tumorigenesis, angiogenesis, invasion, drug resistance and recurrence, which establishes new concepts for cancer diagnosis and treatment.
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1 Clinical observationsGaojushen is a novel anti-cancer drug developed by Xiehe Bio-pharmaceutical Company,Shenyang, China. It is prepared and processed from the filtrate of Staphylococcus aureus culture. The active component contained in it has been shown to be a SEC superantigen that is a metabolite of the culture.This superantigen is marked by its ability to stimulate T cells at a high frequency, thereby giving rise to potent cell-mediated immunological responses and producing a large variety of cytokines with the final rsult of apoptosis of tumor cells. The drug was approved for trial prodoction in 1994 by the Center of the State Evaluation and Review of New Drugs,China,and was licenced for marketing by 1996 after finishing the phase III clinical trial.