食管鳞癌干细胞相关标志物的研究进展

食管鳞癌是我国最常见一种恶性肿瘤,其发病率和死亡率一直处于恶性肿瘤的前列.近年来,愈来愈多证据支持在包括ESCC恶性实体瘤中肿瘤干细胞的存在,并与其不良生物学行为及药物耐受密切相关.肿瘤干细胞标志物在分离肿瘤干细胞起着重要作用,其研究有助于认识和理解肿瘤发生发展的机制,指导肿瘤的临床治疗.     

食管鳞癌干细胞的鉴定及其生物学特性的研究

目的 探讨食管鳞癌细胞(ECCs)的干细胞特性.方法 将ECCs于无血清培养液(SFM)中培养,将其中可悬浮生长并形成的细胞球取出,制成单细胞悬液,以p75NTR为抗原标记细胞后进行流式细胞仪检测,观察其中p75NTR阳性细胞的比例.结果 ECCs可在SFM中悬浮生长并形成细胞球,其形成细胞球的比例为3.6%～17.0%.悬浮生长的细胞中p75NTR阳性细胞比例为16.25%.结论 ECCs在SFM中可悬浮生长并形成细胞球,其中的p75NTR阳性细胞具有干细胞的某些特性,其可作为食管鳞癌干细胞的标记之一.     

食管鳞癌肿瘤相关抗原磷酸甘油酸激酶1的鉴定

目的:鉴定新的食管鳞癌肿瘤相关抗原.方法:食管癌EC0156细胞总蛋白先经亚组分预分离,有效富集胞质、胞膜和胞核等组分蛋白;胞质组分蛋白经SDS-PAGE分离后分别与食管癌患者血清或健康志愿者血清共孵育,分离血清结合蛋白条带;胶内酶解阳性蛋白条带,肽段经色谱分离后用SynaptTM HDMS质谱鉴定.候选蛋白进一步Western blot经免疫组化验证.结果:总蛋白经亚组分分离后,不同组分蛋白均得到有效富集.食管癌患者血清能与EC0156细胞胞质蛋白结合,即选择性识别肿瘤相关抗原.其中,43kDa蛋白条带与食管癌血清(41.4%,12/29)和对照(3.6%,1/28)结合阳性率具有明显差异.从该蛋白条带中共鉴定到磷酸甘油酸激酶、β-actin、蛋白酶体26s亚基、S-腺苷高半胱氨酸水解酶和磷酸核糖酰氨基咪唑羧化酶5个高可信度蛋白.磷酸甘油酸激酶(PGK1)定位于胞质和胞核,在食管癌组织中高表达(69.23%,18/26).结论:改良血清蛋白质组分析策略(mSERPA)可有效分离鉴定肿瘤相关抗原.PGK1是食管癌候选肿瘤相关抗原,在食管癌发生发展中可能发挥重要作用.     

食管鳞癌的病因学研究进展

食管癌是一种由多因素调控多阶段发展的疾病。近年来食管癌研究虽然在流行病学、病因学、早期诊断及综合治疗等方面取得一定进展,但其防治工作依然严峻。食管鳞癌是中国食管癌最主要的组织学类型,本文对食管癌,尤其是食管鳞癌的病因学研究作一综述。     

Wnt信号通路与消化道肿瘤关系的研究进展

Wnt信号通路对控制胚胎发育起着重要作用,其异常激活参与了人类多种肿瘤的发病过程,与消化道肿瘤有着密切关系.而Wnt信号通路的拮抗剂能阻滞信号转导,抑制Wnt2信号通路的异常激活,可望为将来抗肿瘤治疗提供一条新的途径.     

Smad4与原发性食管鳞癌关系的研究进展

食管鳞癌是人类常见的消化系统恶性肿瘤,多发于中老年人群,其形成是多因素作用、多基因变化和多阶段发展的过程。食管上皮的癌变是细胞分化异常、增殖过度与凋亡受阻的结果。转化生长因子-β(TGF-β)是一种多功能的细胞因子,对细     

食管鳞癌免疫治疗相关基因鉴定

目的 通过肿瘤免疫浸润分析食管鳞癌基因集表达谱,鉴定食管鳞癌(esophageal squamous cell carcinoma, ESCC)发生、发展相关免疫基因。方法 基于clusterProfiler算法和肿瘤相关数据库处理分析GSE20347食管鳞癌的基因芯片表达数据。结果 通过基因集数据分析,共得到15个免疫相关通路及核心基因,免疫浸润分析提示多种免疫细胞与核心基因表达水平存在相关性。结论 ATAD5、ATM、EHMT2、PTPN14、UTP18及与其显著相关的免疫细胞可能是ESCC免疫相关研究的新靶点。     

p75NTR阳性人食管鳞癌细胞的干细胞特性研究

目的探讨p75NTR阳性人食管鳞癌细胞的干细胞特性。方法取15例新鲜人食管鳞癌组织制成单细胞悬液,分别获取p75NTR阳性和p75NTR阴性细胞,进行Transwell侵袭试验、耐化疗药物试验及裸鼠成瘤试验。结果15例新鲜人食管鳞癌组织中有7例发现p75NTR表达,其阳性表达率最高为10.37%,p75NTR阳性和p75NTR阴性细胞在侵袭性、对化疗药物的耐受能力及致瘤能力上差异有统计学意义。结论 p75NTR阳性较p75NTR阴性食管鳞癌细胞具有更强的侵袭性、耐化疗能力及致瘤能力,可能富集人食管鳞癌干细胞。     

干细胞与Barrett食管的研究进展

<正>干细胞是一组自我更新、长期稳定分化的细胞群体。Barrett食管(Barrett esophagus,BE)是指食管远端黏膜上皮发生改变,正常的复层鳞状上皮被化生的肠型柱状上皮所替代的一种病理现象。BE是食管腺癌(esophageal adenocarcinoma,EAC)和部分胃-食管连接处腺癌的癌前病变。BE通常发生在慢性的胃食管反流病(gastroesophageal reflux     

STAT3信号蛋白与食管鳞癌上皮间质转化的关系及其意义

目的:探讨食管鳞癌中STAT3、p-STAT3蛋白表达与食管鳞癌上皮间质转化的关系及其在食管鳞癌浸润转移中的作用.方法:采用免疫组织化学技术检测80例食管鳞癌中STAT3、p-STAT3及上皮间质转化标志物E-cadherin和Vimentin的表达.结果:食管鳞癌组织中STAT3、P-STAT3、E-cadherin和Vimentin蛋白阳性率与癌旁正常组织相比有显著性差异(STAT3: 87.5% vs 70.0%; p-STAT3: 72.5% vs 28.8%; E-cadherin:37.5% vs 78.8%; Vimentin: 48.8% vs 0%,均P<0.01).食管鳞癌组织STAT3、p-STAT3的表达均与E-cadhcrin的表达呈负相关(r=-0.41 0,-0.506;均P=0.000),与Vimentin表达均呈正相关(r=0.293,0.321;P=0.008,0.004),且与癌组织的浸润深度密切相关(均P<0.05).结论:信号蛋白STAT3可能参与了食管鳞癌的上皮间质转化过程,并与食管鳞癌的侵袭转移相关.     

食管鳞癌动物模型的研究进展

建立和应用真实模拟人类疾病的动物模型,从整体水平动态地揭示肿瘤发生机制,从而寻找防治对策和开发治疗新药,是成功开展转化医学研究的关键.食管癌是最高发的恶性肿瘤之一.由于相关活体动物模型研究和开发的相对滞后,对于食管鳞癌的病因、发病机制和相关分子通路缺乏全面系统深入的认识,直接导致无法有针对性地进行早期分子诊断标志物和有...     

Pulmonary tumor thrombotic microangiopathy associated with esophageal squamous cell carcinoma

Pulmonary tumor thrombotic microangiopathy (PTTM) is an uncommon cancer-related complication that has been most frequently reported to be associated with adenocarcinoma. We present a case of PTTM which developed in a 60-year-old man with esophageal carcinoma. One year after definitive treatment of the tumor, he developed pulmonary hypertension. Transbronchial lung biopsy (TBLB) specimens showed fibrocellular intimal proliferation and luminal stenosis of the small pulmonary vessels, which contained squamous cell carcinoma cells. Thus, PTTM associated with esophageal carcinoma was diagnosed. This is the first reported case of PTTM associated with esophageal squamous cell carcinoma. TBLB seemed to be useful for obtaining a definitive diagnosis.     

Expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 in esophageal squamous cell carcinoma

正Objective To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues.Methods From August 2011 to May 2013, 73 patients with ESCC,who received radical resection in the First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospi-     

Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinoma

The association of mast cells with tumor angiogenesis was investigated in patients with esophageal squamous cell carcinoma. Surgical specimens from 48 patients with esophageal squamous cell carcinoma were studied. Mast cells in tumor sections were stained with Alcian blue and safranin O. The number of mast cells was counted under light microscopy and the average count recorded. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. Microvessel density was also counted. We found a significant correlation between mast cell count and microvessel density in patients with esophageal squamous cell carcinoma. Double staining of the microvessels revealed highly angiogenic areas densely populated with mast cells. There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with esophageal squamous cell carcinoma.     

肝癌干细胞的研究进展

肿瘤干细胞已经被证实存在于一些肿瘤组织中,而肝癌干细胞是否存在仍未得到确切的结果.通过实验,研究人员对于肝癌干细胞的来源提出了两个假说:成熟肝细胞的去分化与肝干细胞的"成熟受阻".目前后者是较为公认的肝癌形成途径.同时,为了得到肝癌干细胞存在的直接证据,研究人员一直致力于其表面标志物的研究,希望通过得到理想的标志物来鉴定分选出肝癌干细胞.SP细胞与肝癌干细胞的研究也是目前研究的热点.因此,肝癌干细胞的研究将会对肝癌的诊断和治疗产生重大的意义.     

结直肠癌干细胞研究进展

结直肠癌与其他实体肿瘤一样是我国乃至世界范围的重要疾病负担,其治疗也面临许多挑战.近几年,日益受到重视的癌症干细胞理论似乎可以解释结直肠癌的发生发展、复发转移的细胞学机制.本文就结直肠癌干细胞的研究进展作一综述.     

Polymorphisms of survivin promoter are associated with risk of esophageal squamous cell carcinoma

Purpose  Survivin is undetectable in normal adult tissues, but has been shown to be overexpressed in various cancers and has been regarded as a marker of malignancy. Polymorphisms which increase the expression of survivin are potential risk factors for esophageal carcinogenesis. The aim of this study is to genotype the survivin promoter polymorphisms namely −31G/C, −241T/C, −625G/C, and −644T/C in esophageal squamous cell cancer patients and controls and to identify a possible association between individual genetic variation and susceptibility to esophageal squamous cell carcinoma (ESCC). Methods  The expression of survivin in cancer tissues was detected by semiquantitative RT-PCR. A total of 221 Chinese ESCC patients and 268 cancer-free controls were evaluated for the four polymorphisms in survivin promoter. Polymorphisms were identified using the PCR–RFLP technique (−31G/C, −241T/C) or primer-introduced restriction analysis-PCR assay (−644T/C, −625G/C). Results  Compared with the −625GG genotype, the −625CC genotype was associated with significant elevated risk of ESCC (OR = 2.404, 95% CI = 1.342–4.307). Furthermore, significant difference in survivin expression in esophageal squamous cell cancer tissues was found between subgroups with different −625G/C variants. When we examined the combined effect of the survivin promoter polymorphisms, the haplotypes constructed of −644T/C-−625G/C-−31G/C revealed significant associations with ESCC (global P = 0.0034). −644T-−625C-−31C was a risk haplotype for ESCC (P < 0.001) and −644T-−625G-−31C was a protective haplotype (P = 0.004). Conclusions  Our finding suggested that survivin promoter polymorphisms −625G/C might influence the susceptibility to ESCC in the Chinese population, maybe by influencing survivin expression.     

Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma

Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC) contains a heterogeneous population of cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We show that a minority population of CD44(+) cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. The tumors that arose from purified CD44(+) cells reproduced the original tumor heterogeneity and could be serially passaged, thus demonstrating the two defining properties of stem cells: ability to self-renew and to differentiate. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to play a role in self-renewal in other stem cell types and to be involved in tumorigenesis. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis.