肿瘤血管内皮细胞的免疫学特性

在肿瘤的发展过程中,肿瘤血管起到极为重要的作用,不仅为肿瘤提供营养、而且为肿瘤的转移提供了途径。由于肿瘤血管内皮细胞长期处于肿瘤微环境中,其表型及功能特性都发生了明显的变化,其中包括某些免疫学特性的改变,例如内皮细胞粘附分子表达水平降低、白细胞粘附作用减弱、抗原递呈功能不良、抗自由基损伤能力增强、合成大量的细胞外基质等。由于肿瘤血管内皮细胞是免疫细胞和免疫治疗药物进入肿瘤组织的第一道屏障,因此肿瘤血管内皮细胞的免疫学特性可能与肿瘤细胞逃避免疫监视、抵抗免疫杀伤有关。本文简要综述有关肿瘤血管内皮细胞免疫学特性,并分析这些特性与肿瘤免疫逃逸的关系。     

微环境对肿瘤微血管内皮细胞异质性的影响

肿瘤微血管内皮细胞与正常组织来源的微血管内皮细胞相比，具有明显窗孔结构、对生长因子反应性高、粘附因子表达高等特点，是造成肿瘤血管通透性高且新生旺盛的重要原因，导致肿瘤的快速生长和转移。肿瘤微血管内皮细胞具有异质性，受宿主组织、肿瘤类型及肿瘤微环境的多重影响。了解肿瘤微血管内皮细胞发生、形态及功能上的异质性特点及其可能机制，对进行合理的、个性化的、以血管内皮细胞为靶的抗血管新生治疗意义重大。     

肿瘤干细胞与肿瘤血管异质性*

肿瘤血管新生是肿瘤发生和恶性演进过程中基本的生物学过程。传统的血管生成理论认为肿瘤血管新生主要通过由宿主血管网内皮细胞增殖、迁移长入肿瘤组织或由肿瘤组织募集骨髓中的内皮祖细胞增殖、分化为成熟内皮细胞以构建新生血管,即内皮依赖性血管是肿瘤血供的唯一方式。然而越来越多的研究发现肿瘤的微循环网络是异质性的且肿瘤干细胞在肿瘤血管化过程中具有重要作用。本文就肿瘤干细胞（cancer stem cells,CSCs）对不同肿瘤血管新生模式的作用及其作为肿瘤抗血管生成疗法的潜在靶点做一概述,并对肿瘤干细胞促血管生成研究中待解决的问题进行了展望。      

Endoglin与肿瘤血管生成及在肿瘤研究中的意义

Endoglin是内皮细胞表面与增殖相关的膜抗原，主要表达于肿瘤新生血管内皮细胞，可作为肿瘤诊断、转移、复发和判断预后的早期指标，是治疗人体恶性肿瘤的理想的分子靶位。     

影响肿瘤血管形成的几个因素

肿瘤供血血管为肿瘤细胞的形成起着转运营养和气体交换的作用。从某种意义上来讲,肿瘤血管的形成是机体对肿瘤本身的血管形成机制和抑制血管形成机制的失衡造成的。肿瘤血管的形成包括内皮细胞增殖、释放蛋白酶、降解基底膜、内皮细胞黏附及移行并分化成成熟血管等一系列复杂的过程。许多细胞因子参与肿瘤血管的形成过程,本文着重从内皮素,CD105,血管内皮细胞生长因子,肿瘤干细胞以及新近提出的肿瘤拟血管等方面与肿瘤血管形成关系的机制进行综述。1内皮素与肿瘤血管内皮素(endothelin,ET)是一种由内皮细胞合成的生物活性肽,由21个氨基酸…     

肿瘤相关微淋巴管内皮细胞的研究进展

肿瘤相关微淋巴管内皮细胞在肿瘤的转移扩散过程中起着重要的作用,可能直接影响患者的治疗方式和远期生存率。探索肿瘤相关微淋巴管内皮细胞的形态学、细胞生物学和分子生物学等特征,将为深入研究肿瘤的转移扩散机制提供良好的平台,从而有助于阻止肿瘤细胞的扩散,为临床肿瘤的预防与治疗提供有效依据。近年来,有关肿瘤相关微淋巴管内皮细胞的研究进展很快,且研究内容更加广泛和深入。本文就肿瘤相关微淋巴管内皮细胞的研究进展作一综述,为进一步认识肿瘤相关微淋巴管内皮细胞在肿瘤发生及转移过程中的作用提供参考。     

肿瘤血管内皮细胞异质性分子的研究进展

肿瘤血管与正常血管相比,其发生基础、表现形式及分子表达均存在明显差异,肿瘤血管内皮细胞的分子异质性是肿瘤抗血管生成靶向治疗的理论基础。深入研究肿瘤血管异质性分子对于肿瘤诊断、血管靶向治疗等具有重要意义。本文综述目前肿瘤血管内皮细胞异质性分子的研究进展,为相关研究提供参考。     

整合素与肿瘤血管生成

整合素家族是一类黏附分子,表达于内皮细胞,在肿瘤的血管生成过程中起着极为重要的作用.许多细胞因子促进肿瘤的血管生成是通过整合素的介导作用实现的,先引起整合素表达的变化,进一步引起内皮细胞的增殖、迁移.     

血管内皮细胞与肿瘤转移

肿瘤转移是决定肿瘤病人预后的关键因素,也是恶性肿瘤病人的主要死因,如何阻断肿瘤的浸润转移是治愈肿瘤的关键环节.肿瘤转移是一个多步骤复杂过程,肿瘤细胞必须先脱离原发部位,侵入细胞外基质(ECM),与基底膜(BM)及ECM中一些大分子细胞蛋白成分粘附,并激活细胞合成分泌各种降解酶类,穿透血管壁进入循环系统,再穿透血管外渗到继发部位,与继发部位组织粘附形成克隆,增殖生长而形成转移灶.肿瘤细胞浸润转移与内皮细胞关系较密切.癌细胞产生的胶原酶和肿瘤生长因子(TGF)等能直接或间接引起内皮细胞活化,产生胶原酶原及血小板活化因子(PAF)使癌细胞在血管内形成肿瘤血栓.进而癌细胞产生蛋白分解酶,破坏细胞外基质和血管内皮细胞组成的基底膜,导致癌细胞的浸润及转移.肿瘤血行转移的关键步骤之一是血液中的癌细胞栓子附着在血管内皮上,血小板释放凝集素,使肿瘤细胞与内皮细胞粘附,血管内皮细胞收缩变圆,     

胃肠道肿瘤患者血液中血管生长因子的临床意义

肿瘤的增殖、浸润和转移依赖于血管形成。肿瘤的血管形成是一个复杂的多步骤过程，主要包括毛细血管基底膜局部降解；血管内皮细胞内肿瘤组织迁移并伴随细胞增殖；内皮细胞血管化、分支形成新的毛细血管。这一过程是肿瘤细胞、血管内皮细胞与微环境相互作用是结果，表现为肿瘤细胞与内皮细胞相互作用，内皮细胞与基底膜、细胞外基质的相互作用，多种血管生长因子参与了这一过程。促进血管形成的血管生长因子主要包括血管内皮生长因子……     

Correlation between tumor markers and tumor size

Traditionally diagnosis of tumors is made by histopathology, because tumor markers are not sufficiently specific, and only low rates of positive cases have been observed. To induce free release of tumor markers into the blood, the IM injection of vitamin A and infrared-ray hyperthermia was used in 203 cancer patients. Blood samples were collected periodically to determine the levels of CEA, ferritin (FT), alpha-fetoprotein, sialic acid, and the ratio of ferritin to serum iron (FT/Fe). The analysis of each released tumor marker led to an increase in the rate of positive interpretations, indicating a linear correlation between tumor marker and tumor size. As a result of the evaluation of a combination assay of tumor markers using release induction, the rates of positive cases for any three of five markers were increased to 53, 65, and 94% in correlation with an increase in tumor size.     

Monitor tumor burden with circulating tumor DNA

There is a need to identify better biomarkers to monitor diseases and/or assess therapeutic responses. For those with cancer, one can identify DNA fragments that contain somatic mutations originating in the tumor DNA in plasma or serum. There have been several early studies suggesting that advances in sequencing technologies will allow identification of somatic genomic alterations that can be used to monitor tumor dynamics. Dawson et al. investigated circulating cell-free DNA carrying tumor specific alterations in patients with breast cancer. The authors compared CT imaging from 30 women with metastatic breast cancer receiving treatment, using two assays for circulating tumor DNA, CA 15-3, and CTCs. Taken the two methods together circulating tumor DNA was detected in 29 or 30 women (97%) and 115 of 141 plasma samples (82%). Circulating tumor DNA levels showed a greater dynamic range and greater correlation with changes in tumor burden than did CA 15-3 or CTC. The relatively small study showed that circulating tumor DNA has a superior sensitivity to other circulating biomarkers and a dynamic range that correlates with tumor burden.     

Circadian-rhythm of tumor growth in non-vascularized tumor

Circadian-Rhythms of tumor growth rates of Walker-256 implanted in the dorsum side of hind paw of Wistar rats (Male 5-6 weeks age) were observed. Tumor size was measured at 7 A.M. and 7 P.M. The tumor growth rate was determined by the following method. Rday = T (P.M.)/T (A.M.). Rnight = T (A.M.)/T (previous P.M.). Rday and Rnight: Tumor growth rate during day and night, respectively. T: Tumor size. The tumor growth rate, for those less than 750 mm3 in size and in which tumor vessels did not form yet, was 0.10 +/- 0.5 on Rday, 0.29 +/- 0.12 on Rnight (p less than 0.05). Tumors of more than 1,500 mm3 forming tumor vessels did not show a significant difference in the degree of the tumor growth rate (Rday: 0.14 +/- 0.07; Rnight: 0.212 +/- 0.05) (p greater than 0.05). Tumors in which vessels were injured and showed microvascular disturbance due to MMC (A. i) or thermochemotherapy using warmed physiological saline injected into tumor vessels after chemotherapy, were damaged on Rday and enhanced on Rnight for 3-7 days after these kinds of treatment. The tumor in unformed tumor vessels or damaged types showed, rapid size increase at night. Therefore, the Circadian-Rhythm tumor vessels in microtumor or damaged tumor may be treated with antimetabolic agents such as 5-FU at night for inhibition of microtumor or micrometastatic tumor.     

肿瘤血管生成调节与肿瘤治疗

肿瘤血管生成是一个非常复杂的过程，涉及到多种因子的调节。针对肿瘤血管生成的治疗对策在目前肿瘤治疗中具有十分重要的意义。本文就影响肿瘤血管生成的各种调节因子、抗血管生成的主要治疗靶标及研发现状作一综述，为肿瘤治疗的抗血管生成新靶标的设计研究提供信息。     

肿瘤抗原在肿瘤研究中的应用

近年来随着肿瘤抗原筛选鉴定方法的多样化,已鉴定出了大量的肿瘤抗原,抗原的分类越来越全面,肿瘤抗原的基础性研究已经深入到其他学科,肿瘤抗原的检测诊断则在临床上应用越来越广泛,而针对不同抗原的免疫治疗也更加具体可行.     

Inducing tumor immunity by specific tumor antigens.

A handy experimental model for testing anti-tumor agents and for studying tumor immunity is the use of Walker 256 carcinosarcoma in Long-Evans hooded rats. This neoplasm is so easily transplantable and growth is so rapid that a large series of animals can be studied in a relatively short period of time.     

The inhibition of tumor growth by tumor mass

Evidence suggests that a tumor behaves, in its pattern of growth, like an integrated organ rather than a collection of independently growing cells. Tumor growth tends to slow progressively as size increases and to undergo compensatory growth after partial resection. Consequently, therapies that reduce tumor mass may tend to accelerate the growth of the remaining tumor and tumor metastases. An approach to therapy based upon a simulated increase in tumor mass may be worthy of consideration.     

肿瘤微环境中的炎性机制与肿瘤转移

炎性微环境是肿瘤微环境中影响肿瘤复发转移的关键因素之一.肿瘤炎性微环境可以通过调节上皮细胞向间充质细胞转变,启动肿瘤转移;可以通过降解细胞外基质从而破坏细胞外基质膜促进肿瘤细胞的侵袭;同时,炎性微环境促进肿瘤血管的新生为肿瘤的发生发展提供保障.