非小细胞肺癌外周血树突状细胞含量与血管内皮生长因子浓度的关系

目的检测非小细胞肺癌(NSCLC)外周血树突状细胞(DC)含量和血管内皮生长因子(VEGF)水平,探讨二者间的相互关系.方法采用流式细胞技术对55例NSCLC、13例肺部良性病变及12例正常人外周血DC含量进行检测,并用ELISA法检测血浆VEGF浓度.结果肺部良性病变者的外周血DC含量和VEGF浓度与正常人相比无显著差异(P＞0.05),但NSCLC患者外周血DC含量显著降低,而血浆VEGF浓度显著增高(P＜0.05～0.01).NSCLC外周血DC含量及VEGF浓度与性别、年龄、病理类型及分化程度无明显关系,但与临床分期和淋巴结转移有密切关系(P＜0.05).外周血DC含量与VEGF浓度呈负相关.结论 NSCLC外周血DC含量降低和VEGF浓度增高与肺癌恶性程度有密切关系.NSCLC过表达VEGF可能是导致DC分化受阻的主要原因之一.     

非小细胞肺癌外周血中树突状细胞含量降低及其意义

目的　探讨非小细胞肺癌 (NSCLC)外周血中树突状细胞 (DC)含量及其与肺癌临床病理特征的关系。方法　采用流式细胞技术检测了 4 1例NSCLC、8例肺部良性病变及 12例正常人外周血中的DC。结果　肺部良性病变者的外周血中DC含量与正常人相比无明显差异 (P >0 .0 5 ) ,但NSCLC患者DC含量显著降低 (P <0 .0 1)。上述三组的外周血DC与单个核细胞比值 (DC/PBMC)分别为 0 .6 0± 0 .0 5 %、0 .83± 0 .0 8%、1.0 2± 0 .11% ,DC计数分别为 2 1.0 0± 3.0 4× 10 6/L、2 9.0 0± 4 .0 1×10 6/L、16 .0 0± 1.5 2× 10 6/L。NSCLC外周血中DC含量与性别、年龄及病理类型无关 ,但与分化程度、淋巴结转移、临床分期及远道转移呈负相关 (P <0 .0 5 )。结论　NSCLC外周血中DC分化成熟严重缺陷 ,血中DC含量与肺癌恶性程度有关。     

血管内皮生长因子对非小细胞肺癌血道转移的影响

目的 探讨血管内皮生长因子（VEGF）含量对非小细胞肺癌（NSCLC）血道转移的影响。方法 外周血中细胞角蛋白（CK）阳性细胞经磁性细胞分选技术分离后,采用细胞学、免疫组化及免疫荧光染色对其中的肺癌细胞进行特性分析。外周血肺癌细胞含量按已建立的流式细胞仪检测方法作定量分析。VEGF含量采用ELISA测定。结果 外周血肺癌细胞具有明显的核异型,表达端粒酶逆转录酶（hTERT)及上皮细胞标志CK,可被抗人NSCLC特异性单抗S5A10－2染色,但不表达白细胞抗原CD34及CD45。154例NSCLC患者中,外周血肺癌细胞阳性44例,阳性率为28．6％。癌细胞阳性率与病期进展相关。NSCLC患者血浆VEGF含量显著高于健康人及肺部良性疾患者。VEGF含量与肺腺癌的病期进展密切相关。在血循环癌细胞阳性NSCLC患者中,VEGF含量增高者,癌细胞数量显著高于VEGF不增高者。结论 NSCLC患者血浆VEGF明显增高,在血循环癌细胞阳性的患者中,VEGF高表达可促使癌细胞血道转移,表现为血循环癌细胞数量明显增加。     

肺癌患者血浆中血管内皮生长因子与碱性纤维母细胞生长因子表达

目的　研究血管内皮生长因子 (VEGF)与碱性纤维母细胞生长因子 (bFGF)在肺癌患者血浆中表达水平。方法　采用定量免疫酶标 (ELISA)方法 ,检测 92例肺癌患者及肺部良性疾病血浆中VEGF与bFGF的含量。结果　 84例肺癌与 7例肺部良性疾病血浆中VEGF含量分别为 2 0 1.5± 183.0pg/ml,10 2 .5± 6 2 .5pg/ml,两者差异有显著性 (P <0 .0 5 ) ;其中 4 4例腺癌和 7例小细胞癌的VEGF含量分别为 2 0 2 .3± 177.0pg/ml、381.4± 314 .3pg/ml,与其肺部良性疾病比较 ,差异均有显著性 (分别为P <0 .0 5、P <0 .0 0 1)。在 5 6例肺癌与 4例肺部良性疾病血浆中bFGF含量分别为 4 5 .4± 2 3.9pg/ml,5 0 .4± 2 7.2pg/ml,两者差异无显著性。结论　在肺癌患者血浆中VEGF的含量明显高于肺部良性疾病的含量 ,其中腺癌和小细胞肺癌差异有显著性。而肺癌与肺部良性疾病无明显差异     

原发性肺癌患者外周血内皮抑素检测意义

目的 :研究原发性肺癌患者外周血内皮抑素 (endostatin)的含量水平与肺癌临床病理因素的关系。方法 :用ELISA法对 79例原发性肺癌、8例肺部良性疾病及 2 0例健康人血浆内皮抑素含量进行分析。结果 :血浆内皮抑素含量在原发性肺癌、肺部良性疾病及健康人分别为 (9 3± 5 7)pg mL、(6 3±2 5 )pg mL、(4 9± 3 2 )pg mL ,肺癌明显高于肺部良性疾病和健康人 ,P <0 0 5 ;血浆内皮抑素含量在Ⅰ、Ⅱ、Ⅲ、Ⅳ期肺癌中分别为 (6 6± 4 3)pg mL、(7 1± 5 5 )pg mL、(8 7± 6 0 )pg mL、(10 6± 4 5 )pg mL ,血浆内皮抑素含量与肺癌临床分期有关 ,P <0 0 5 ;年龄≥ 6 0岁肺癌患者血浆内皮抑素含量为 (7 9± 4 2 )pg mL ,年龄 <6 0岁为 (10 4± 5 6 )pg mL ,后者明显高于前者 ,P <0 0 1。结论 :原发性肺癌患者外周血内皮抑素含量水平显著高于正常对照 ,且与肿瘤分期和淋巴结转移有关     

原发性肝癌患者血清高水平VEGF的意义

目的:研究血清血管内皮生长因子(vascularendothelial growth factor, VEGF)水平与肝癌临床病理及肿瘤病理学之间的关系。方法:应用VEGF 165定量夹心ELISA法测定30 例正常人、30 例肝硬化和45例肝癌患者外周血清中VEGF的水平,并结合临床及肿瘤病理学的特点进行统计学分析。结果:正常人血清VEGF水平为(153±71)pg/mL,分布范围为(6~371) pg/mL;肝硬化患者血清VEGF水平为(158±67)pg/mL,分布范围为(4~352) pg/mL;45例肝癌患者血清VEGF为(312±206) pg/mL,分布范围为(34~968)pg/mL。肝癌患者的外周血VEGF水平显著高于正常人和肝硬化患者,P<0. 01。高水平的血清VEGF与肝癌的大小、包膜的不完整以及转移与复发有关, P<0. 01,而与肿瘤的分化程度无关, P>0 .01。当肿瘤发展到第Ⅳ期,血清VEGF水平显著升高, P<0. 01。结论:血清VEGF高水平是肝细胞肝癌具有血管侵犯和转移潜在危险的指标,预示不良的预后。     

外周血循环癌细胞定量分析及其临床意义探讨

目的探讨流式细胞仪定量分析外周循环血中癌细胞的临床意义.方法外周血经Ficoll梯度离心分离单核细胞组分,后者用CD45、细胞角蛋白(CK)及肺癌单克隆抗体(2F7/S5A)染色后,应用流式细胞仪检测CD45-CK+2F7/S5A+细胞,计算每升血中上述细胞含量,定量分析143例肺癌,26例良性肺部疾病,20例健康对照外周血中的癌细胞.结果 20例健康对照均为阴性,26例良性肺部疾病2例阳性,143例肺癌患者60例阳性,阳性可测率42%,阴性可测率95.7%,检测阳性细胞含量的平均数为0.722×106/L.M1组阳性率高于M0组,两且差异有显著意义P=0.000,阳性率与期别正相关,P=0.024.阳性组和阴性组的中位生存期分别为17.0月及18.8月,生存率阳性组稍低,但无统计学意义.结论应用流式细胞仪定量分析肺癌患者外周循环血中CD45-CK+2F7/S5A+细胞反应肺癌惠者外周循环血中的微量癌细胞,有助于判断肺癌的转移倾向和预后.     

非小细胞肺癌患者肿瘤组织和血清中VEGF相关关系的研究

目的　本研究拟通过对非小细胞肺癌 (NSCLC)患者肿瘤组织血管内皮生长因子 (VEGF)表达的观察及血清中VEGF水平的检测 ,以探讨肿瘤组织VEGF与血清VEGF的相关关系。方法　用免疫组化LAB -SA(即SP)方法检测 31例NSCLC患者肿瘤组织中的VEGF表达 ;用双抗夹心ELISA法测定上述 31例NSCLC患者术前血清中VEGF水平 ,17例肺良性病变和 2 0例正常人血清作为对照。结果　 31例非小细胞肺癌中 ,肿瘤组织VEGF阳性表达 2 6例 ,占 83.9% ,肿瘤组织VEGF高表达 (3级 +4级 ) 17例 ,占 5 4 .5 % ;血清VEGF高表达 (≥ 4 0 0pg/ml) 16例 ,占 5 1.6 % ,经统计学分析 ,患者肿瘤组织中VEGF高表达率和血清中VEGF水平高表达率无统计学差异 ,P >0 .0 5 ;秩相关分析 ,rs’ =0 .85 92 ,P <0 .0 1,二者呈正相关关系。结论　血清中VEGF水平同肿瘤组织中VEGF表达呈同向变化 ,即肿瘤组织中VEGF含量越高 ,血清中VEGF水平越高 ;肿瘤组织中VEGF含量越低 ,血清中VEGF水平越低。血清中VEGF水平的测定有可能替代肿瘤组织中VEGF的检测 ,成为一种快捷、简便的检测方法 ,尽早为临床选择治疗方法及判断预后提供依据。     

NSCLC微波消融前后血清VEGF、Arg-1、iNOS水平变化及其相关性

目的 探讨微波消融治疗非小细胞肺癌(NSCLC)的疗效,分析微波消融前后NSCLC患者血清血管内皮生长因子(VEGF)、精氨酸酶-1(Arg-1)、诱导型一氧化氮合酶(iNOS)浓度的变化及三者之间的关系.方法 选取30例健康体检者作为对照组,30例晚期NSCLC患者为试验组,用酶联免疫吸附试验(ELISA)法检测健康体检者、晚期NSCLC患者微波消融术前及术后第1天、第3天、1个月血清VEGF、Arg-1、iNOS浓度.结果 微波消融治疗晚期NSCLC的有效率为33.3％ (10/30),疾病控制率为70.0％(21/30).微波消融术前NSCLC患者血清VEGF、Arg-1、iNOS浓度分别为(816.56±13.26)pg/ml、(5.17±0.20) ng/ml、(544.18±13.93) pg/ml,明显高于对照组的(93.43±9.93) pg/ml、(1.08±0.05) ng/ml、(8.08-±0.33) pg/ml,差异均有统计学意义(t=239.093,P＜0.001;t=110.359,P＜0.001;t=210.792,P＜0.001).晚期NSCLC患者微波消融术后第1天、第3天、1个月血清VEGF浓度分别为(708.41±10.49)pg/ml、(592.63±7.25) pg/ml、(521.91±8.32) pg/ml,均较治疗前明显降低(均P ＜0.05);Arg-1浓度分别为(5.95±0.10) ng/ml、(7.02±0.13) ng/ml、(7.67±0.92) ng/ml,均较治疗前明显升高(均P ＜0.05);iNOS浓度分别为(453.01±9.48)pg/ml、(393.21±9.42) pg/ml、(352.60±8.31)pg/ml,均较治疗前明显降低(均P＜0.05).NSCLC患者治疗前血清iNOS与VEGF表达呈正相关(r =0.379,P=0.039),Arg-1与VEGF表达呈负相关(r=-0.556,P=0.001),iNOS与Arg-1表达无关(r=-0.238,P=0.205).结论 微波消融是一种有效的NSCLC局部治疗手段,除可直接杀灭癌细胞外,亦可影响VEGF、Arg-1、iNOS表达水平,VEGF与iNOS和Arg-1有一定相关性,而iNOS与Arg-1无关.微波消融可在一定程度上改变肿瘤微环境,刺激机体产生抗肿瘤免疫.     

非小细胞肺癌患者血浆D-二聚体水平及其临床意义

目的 探讨非小细胞肺癌（NSCLC）患者的血浆D-二聚体水平及其临床意义。方法采用酶联免疫吸附法（ELISA）检测215例NSCLC患者治疗前后、90例良性肺部疾病患者及60例健康对照者的血浆D-二聚体水平。随访1年,记录NSCLC患者术后肿瘤复发转移率,计算NSCLC患者化疗后的中位生存时间。结果NSCLC患者血浆D-二聚体水平为（1.73±0.26）mg／L,显著高于良性肺部疾病患者的（0.26±0.03）mg／L和健康对照者的（0.23±0.01）mg／L,差异有统计学意义（P＜0.05）。Ⅲ～Ⅳ期NSCLC患者D-二聚体水平为（2.31±0.34）mg／L,明显高于Ⅰ～Ⅱ期NSCLC患者的（0.87±0.38）mg／L,差异有统计学意义（P＜0.05）。105例NSCLC患者术后血浆D-二聚体的阳性率为28.6%,明显低于术前的49.5%（P＜0.05）;而110例NSCLC患者化疗前、后血浆D-二聚体的阳性率差异无统计学意义。术前血浆D-二聚体阳性患者的肿瘤复发或转移率为28.8％,明显高于术前阴性患者的5.7％（P＜0.05）。化疗前血浆D-二聚体阳性患者的中位生存时间为8.7个月,显著低于阴性患者的12.8个月（P＜0.05）。结论 NSCLC患者的血浆D-二聚体水平与肿瘤分期有关,可能有助于评估手术疗效及预测预后。     

肿瘤干细胞的研究进展

肿瘤干细胞是存在于肿瘤中的一小部分具有干细胞性质的细胞群,具有高度的致瘤性和耐药性。同正常干细胞一样,肿瘤干细胞具有无限的自我更新和多向分化的潜能,使肿瘤在体内不断扩大或形成新的肿瘤,导致肿瘤复发和转移。肿瘤干细胞的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。     

肿瘤干细胞的研究进展

肿瘤干细胞是存在于肿瘤中的一小部分具有干细胞性质的细胞群,具有高度的致瘤性和耐药性。同正常干细胞一样,肿瘤干细胞具有无限的自我更新和多向分化的潜能,使肿瘤在体内不断扩大或形成新的肿瘤,导致肿瘤复发和转移。肿瘤干细胞的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。     

肿瘤细胞的集体行为

单细胞的高度相关性是维持单细胞存在的必要条件。肿瘤细胞表现出交流、纠缠、选择、竞争、可塑、适应、融合、迁移、种植、变异、进化和退化等不同的集体行为,维持肿瘤作为独立器官的发生和发展。研究肿瘤细胞的集体行为有助于了解"肿瘤社会"的生物属性,改变传统对癌症治疗的策略。     

Tissue mast cells in breast cancer

Summary The total number of mast cells and the number of such cells observed within and at the periphery of invasive breast cancers from 424 patients enrolled in protocol 4 of the National Surgical Adjuvant Breast Project were correlated with 38 other pathologic and 6 clinical features. High total mast cell counts as well as those within and at the periphery of the cancers were found to be significantly (p.05) associated with a patient age less than 50 years and the degree of tumor lymphoid cell reaction. The latter has also been found to be related to young age and other pathologic characteristics related to mast cell content. This suggests that the mast cells may simply represent another cell type of this reactive change. No differences in 10 year disease-free survival were detected in patients without mast cells and those exhibiting varying numbers of such cells. This information indicates that identifiable mast cells do not represent a prognostic pathologic discriminant in patients with breast cancer. However, this does not unequivocally exclude a role of mast cell secretory products, since only intact and not degranulated or disrupted forms of these cells can be counted.     

Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.     

Chemoresistant colorectal cancer cells and cancer stem cells mediate growth and survival of bystander cells

Background:

Recent studies suggest that cancer stem cells (CSCs) mediate chemoresistance, but interestingly, only a small percentage of cells in a resistant tumour are CSCs; this suggests that non-CSCs survive by other means. We hypothesised that chemoresistant colorectal cancer (CRC) cells generate soluble factors that enhance survival of chemonaive tumour cells.

Methods:

Chemoresistant CRC cells were generated by serial passage in oxaliplatin (Ox cells). Conditioned media (CM) was collected from parental and oxaliplatin-resistant (OxR) cells. CRC cells were treated with CM and growth and survival were assessed. Tumour growth rates were determined in nude mice after cells were treated with CM. Mass spectrometry (MS) identified proteins in CM. Reverse phase protein microarray assays determined signalling effects of CM in parental cells.

Results:

Oxaliplatin-resistant CM increased survival of chemo-naive cells. CSC CM also increased growth of parental cells. Parental and OxR mixed tumours grew larger than tumours composed of parental or OxR cells alone. Mass spectrometry detected unique survival-promoting factors in OxR CM compared with parental CM. Cells treated with OxR CM demonstrated early phosphorylation of EGFR and MEK1, with later upregulation of total Akt .We identified progranulin as a potential mediator of chemoresistance.

Conclusion:

Chemoresistant tumour cells and CSCs may promote resistance through soluble factors that mediate survival in otherwise chemosensitive tumour cells.     

上皮间质转化和肿瘤干细胞

最近,两个新的概念出现在肿瘤生物学中：上皮间质转化（epitheilal-mesenchymal transition,EMT）和肿瘤干细胞（cancer stem cells,CSCs）。EMT不仅赋予细胞迁移和侵袭特征,还可使肿瘤细胞获得自我更新能力而具有干细胞的特性,从而促进CSCs的产生。本文讨论EMT和CSCs之间的联系、EMT获得干细胞特征促进CSCs产生、EMT是形成CSCs的重要环节及二者在干细胞巢中的转化,并分析影响EMT和CSCs的因素。研究EMT在肿瘤发生中的作用,与CSCs理论相融合,从而可能发现新的肿瘤靶向治疗。     

BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells

Cancer stem cells (CSCs) are initiating cells in colorectal cancer (CRC). Colorectal tumours undergo epithelial to mesenchymal transition (EMT)-like processes at the invasive front, enabling invasion and metastasis, and recent studies have linked this process to the acquisition of stem cell-like properties. It is of fundamental importance to understand the molecular events leading to the establishment of cancer initiating cells and how these mechanisms relate to cellular transitions during tumourigenesis. We use an in vitro system to recapitulate changes in CRC cells at the invasive front (mesenchymal-like cells) and central mass (epithelial-like cells) of tumours. We show that the mesoderm inducer BRACHYURY is expressed in a subpopulation of CRC cells that resemble invasive front mesenchymal-like cells, where it acts to impose characteristics of CSCs in a fully reversible manner, suggesting reversible formation and modulation of such cells. BRACHYURY, itself regulated by the oncogene β-catenin, influences NANOG and other 'stemness' markers including a panel of markers defining CRC-CSC whose presence has been linked to poor patient prognosis. Similar regulation of NANOG through BRACHYURY was observed in other cells lines, suggesting this might be a pathway common to cancer cells undergoing mesenchymal transition. We suggest that BRACHYURY may regulate NANOG in mesenchymal-like CRC cells to impose a 'plastic-state', allowing competence of cells to respond to signals prompting invasion or metastasis.     

上皮间质转化和肿瘤干细胞

最近,两个新的概念出现在肿瘤生物学中:上皮间质转化(epitheilal-mesenchymal transition,EMT)和肿瘤干细胞(cancer stem cells,CSCs)。EMT不仅赋予细胞迁移和侵袭特征,还可使肿瘤细胞获得自我更新能力而具有干细胞的特性,从而促进CSCs的产生。本文讨论EMT和CSCs之间的联系、EMT获得干细胞特征促进CSCs产生、EMT是形成CSCs的重要环节及二者在干细胞巢中的转化,并分析影响EMT和CSCs的因素。研究EMT在肿瘤发生中的作用,与CSCs理论相融合,从而可能发现新的肿瘤靶向治疗。     

Pancreatic cancer stem cells

Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever.