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microRNAs(miRNAs)是一类转录后调控基因表达的内源性非编码微小RNA。愈来愈多的研究显示,miRNAs在肿瘤免疫应答中发挥重要调控作用。一方面,miRNAs通过转录后调控ICAM(intercellular adhesion molecule)、B7(CD80/86)和HLA—G(human leucocyte antigen—G)等肿瘤表面分子的表达,影响肿瘤的免疫原性;另一方面,miRNAs通过平衡肿瘤局部的细胞因子微环境或调控肿瘤免疫相关细胞的分化、发育及功能发挥,调节机体抗肿瘤免疫应答。为后续深入研究肿瘤与宿主的相互作用机制,以及发展更有效的肿瘤生物治疗手段,就目前miRNAs在肿瘤免疫中的调控作用的研究进展做一综述。 相似文献
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肥大细胞是人体主要免疫细胞之一,因其作为导致过敏反应发生的最直接效应细胞而著称.肥大细胞最主要的结构特征为其胞内含有大量嗜碱性颗粒,该颗粒内又富含种类众多的生物活性物质,包括组胺、血管内皮生长因子(vascular endothelial growth factor,VEGF)、成纤维细胞生长因子(fibroblast... 相似文献
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Bosslet K. Czech J. Seemann G. Monneret C. Hoffmann D. 《Cell biochemistry and biophysics》1994,24(1-3):51-63
A two component system, consisting of a fusion protein and an appropriate prodrug, suited to perform selective tumor therapy
in vivo, is presented. The fusion protein, owing to its humanized carcinoembryonic antigen (CEA)-specific variable region,
specifically binds to CEA-expressing tumors and has an enzymatic activity comparable to human β-glucuronidase. The prodrug
is a nontoxic glucuronide-spacer-derivative of doxorubicin decomposing to doxorubicin by enzymatic deglucuronidation.
In vivo studies in nude mice bearing human CEA-expressing tumor xenografts revealed that 7 d after injection of 20 mg/kg fusion
protein, a high specificity ratio (>100:1) was obtained between tumor and plasma. Injection of 250 mg/kg of prodrug at d 7
resulted in tumor therapeutic effects superior to conventional chemotherapy without any detectable toxicity. These superior
therapeutic effects that were observed using established human tumor xenografts can be explained by the approx 10-fold higher
drug concentrations found in tumors of mice treated with fusion protein and prodrug than in those treated with the maximal
tolerable dose of drug alone. 相似文献
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Diversity of Metabolic Patterns in Human Brain Tumors: Enzymes of Energy Metabolism and Related Metabolites and Cofactors 总被引:5,自引:3,他引:2
Oliver H. Lowry Sosamma J. Berger Joyce G. Carter Maggie M.-Y. Chi Jill K. Manchester Joseph Knor Mary E. Pusateri 《Journal of neurochemistry》1983,41(4):994-1010
Biopsies from 15 human gliomas, five meningiomas, four Schwannomas, one medulloblastoma, and four normal brain areas were analyzed for 12 enzymes of energy metabolism and 12 related metabolites and cofactors. Samples, 0.01-0.25 microgram dry weight, were dissected from freeze-dried microtome sections to permit all the assays on a given specimen to be made, as far as possible, on nonnecrotic pure tumor tissue from the same region. Great diversity was found with regard to both enzyme activities and metabolite levels among individual tumors, but the following generalities can be made. Activities of hexokinase, phosphorylase, phosphofructokinase, glycerophosphate dehydrogenase, citrate synthase, and malate dehydrogenase levels were usually lower than in brain; glycogen synthase and glucose-6-phosphate dehydrogenase were usually higher; and the averages for pyruvate kinase, lactate dehydrogenase, 6-phosphogluconate dehydrogenase, and beta-hydroxyacyl coenzyme A dehydrogenase were not greatly different from brain. Levels of eight of the 12 enzymes were distinctly lower among the Schwannomas than in the other two groups. Average levels of glucose-6-phosphate, lactate, pyruvate, and uridine diphosphoglucose were more than twice those of brain; 6-phosphogluconate and citrate were about 70% higher than in brain; glucose, glycogen, glycerol-1-phosphate, and malate averages ranged from 104% to 127% of brain; and fructose-1,6-bisphosphate and glucose-1,6-bisphosphate levels were on the average 50% and 70% those of brain, respectively. 相似文献
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血小板是巨核细胞产生的无核细胞碎片,其主要功能是参与凝血和止血。近年来,越来越多的研究和临床证据表明,血小板还参与并促进了肿瘤转移。当肿瘤细胞从原位肿瘤组织脱落进入血管后,血小板是其第一个接触到的宿主细胞。作为肿瘤转移微环境中的重要成员,血小板与肿瘤细胞之间相互作用和相互影响。一方面,肿瘤细胞能通过诱导血小板活化和聚集来调节血小板功能;另一方面,血小板能够通过直接接触和释放生物活性介质的方式,促进肿瘤转移。大量的研究结果表明,血小板主要通过以下几条途径促进肿瘤转移:1)降低血液流体剪切力对肿瘤细胞造成的机械损伤;2)帮助肿瘤细胞逃避免疫监视;3)促进肿瘤细胞在血管内的迁移和停滞;4)促进肿瘤细胞上皮间质转化;5)促进肿瘤细胞外渗;6)构建适合肿瘤细胞生存的转移生态位。因此,靶向血小板与肿瘤细胞相互作用成为潜在的肿瘤治疗策略。本文以国内外最新研究进展为基础,综述血小板在肿瘤转移不同阶段发挥的作用,以及抗血小板药物在肿瘤治疗中的应用。 相似文献
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PCR直接测序方法及其在肿瘤研究中的应用 总被引:4,自引:0,他引:4
PCR直接测序技术是PCR扩增与核酸测序技术相结合的一种方法.根据此技术的原理,建立了一种以PCR扩增引物为测序引物,α-35S dATP直接掺入,Taq DNA聚合酶直接测序PCR扩增产物的方法.实验表明:该方法简便、快速、稳定.用此方法对人食管癌组织中的抗癌基因p53进行了突变测序分析,发现食管癌组织中p53存在点突变,插入、丢失移码突变.并用此方法对人和恒河猴的p53内含子序列进行了测定,发现猴第5内含子为81个核苷酸,第8内含子为92个核苷酸. 相似文献
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Recently, phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018. Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process; proving to be a powerful technique in the screening of peptide with high affinity and selectivity. In this review, we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods. We will then discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and overexpressed receptors on cancer cells identified through phage display screening. We will also discuss the current challenges and future outlook for targeting peptidebased therapeutics in the clinics. 相似文献
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中性粒细胞是机体外周血中数量最多的白细胞,在人体非特异性免疫系统中发挥着十分重要的作用.早期的研究认为,中性粒细胞能通过分泌细胞因子和产生活性氧等物质杀伤肿瘤.然而随着研究的深入,发现肿瘤微环境中的中性粒细胞对肿瘤的发展起到促进的作用.浸润性中性粒细胞产生的细胞因子和趋化因子能影响肿瘤微环境中炎症细胞的招募和激活,为肿瘤的发展提供良好的免疫抑制微环境,调控肿瘤的生长、转移和血管生成,还在肿瘤患者预后评估方面发挥着重要的作用. 相似文献
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细胞源性异种移植(cell line-derived xenografts,CDX)与原发肿瘤相比失去了肿瘤的异质性和基因的多样性,在临床前的实验中不能有效评估肿瘤药物的疗效和安全性,致使临床药物高消耗而没有达到治疗疾病的目的,严重阻碍了临床药物的发展;人源性肿瘤组织异种移植(patient-derived tumor xenografts,PDTX)保持了原发肿瘤的分子学、基因学和病理学特征,而且经过在小鼠体内传代它仍保持了原发肿瘤的这些特性,为肿瘤的个体化治疗提供了更好的模型。PDTX模型的这些特性与CDX模型相比在肿瘤的个体化治疗方面更具有指导意义。本文将就PDTX模型的特征及其在肿瘤研究领域中的应用作系统阐述。 相似文献
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黏附分子CD24在肿瘤转移中作用 总被引:6,自引:0,他引:6
CD24属糖基磷脂酰肌醇锚蛋白。作为P-选择素配体的黏附分子,其可调节B细胞发育和神经发生。研究显示,CD24高表达在多种肿瘤细胞表面,参与肿瘤的发生发展。已通过体外试验和动物模型证实CD24对多种肿瘤生长和转移相关的肿瘤细胞特性具有调节作用;结合人肿瘤组织研究显示,CD24和乳腺癌、前列腺癌、胰腺癌及肝内胆管癌等肿瘤患者的生存率及预后密切相关。因此,以CD24为靶向的肿瘤诊断和治疗有着诱人的临床应用前景。 相似文献
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Hyaluronan promotes tumor lymphangiogenesis and intralymphantic tumor growth in xenografts 总被引:2,自引:0,他引:2
Hyaluronan (HA), a high molecular weight glycosaminoglycan in the extracellular matrix, has been implicated in the promotion of malignant phenotypes, including tumor angiogenesis. However, little is known about the effect of HA on tumor-associated lymphangiogenesis. In this study, mouse hepatocellular carcinoma Hca-F cells combined with or without HA were injected subcutaneously into C3H/Hej mice, then angiogenesis and lymphangiogenesis of implanted tumors were examined by immunostaining for plateletendothelial cell adhesion molecule-1 and lymphatic vascular endothelial hyaluronan receptor-1 respectively. Interestingly, we found HA promotes tumor lymphangiogenesis and the occurrence of intratumoral lymphatic vessels, but has little effect on tumor angiogenesis. Moreover, HA also promotes intralymphatic tumor growth, although it is not sufficient to potentiate lymphatic metastasis. These results suggest that HA, which is elevated in most malignant tumor stroma, may also play a role in tumor progression by promoting lymphangiogenesis. 相似文献
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Ziyan Chen Pengyi Guo Xiaozai Xie Haitao Yu Yi Wang Gang Chen 《Journal of cellular and molecular medicine》2019,23(1):59-69
Cholangiocarcinoma (CCA) is a relatively rare malignant and lethal tumour derived from bile duct epithelium and the morbidity is now increasing worldwide. This disease is difficult to diagnose at its inchoate stage and has poor prognosis. Therefore, a clear understanding of pathogenesis and major influencing factors is the key to develop effective therapeutic methods for CCA. In previous studies, canonical correlation analysis has demonstrated that tumour microenvironment plays an intricate role in the progression of various types of cancers including CCA. CCA tumour microenvironment is a dynamic environment consisting of authoritative tumour stromal cells and extracellular matrix where tumour stromal cells and cancer cells can thrive. CCA stromal cells include immune and non‐immune cells, such as inflammatory cells, endothelial cells, fibroblasts, and macrophages. Likewise, CCA tumour microenvironment contains abundant proliferative factors and can significantly impact the behaviour of cancer cells. Through abominably intricate interactions with CCA cells, CCA tumour microenvironment plays an important role in promoting tumour proliferation, accelerating neovascularization, facilitating tumour invasion, and preventing tumour cells from organismal immune reactions and apoptosis. This review summarizes the recent research progress regarding the connection between tumour behaviours and tumour stromal cells in CCA, as well as the mechanism underlying the effect of tumour stromal cells on the growth of CCA. A thorough understanding of the relationship between CCA and tumour stromal cells can shed some light on the development of new therapeutic methods for treating CCA. 相似文献
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上皮-间质转化(epithelial-mesenchymal transitions,EMT)是上皮细胞向间质细胞转化的现象,不仅参与胚胎发育和正常生理,还参与许多病理过程。同样EMT也参与肿瘤的发生与发展,尤其在促进肿瘤侵袭转移中发挥着重要作用。研究表明,肿瘤细胞借助EMT方式增强肿瘤细胞迁移和运动能力,促进肿瘤的侵袭与转移。在肿瘤侵袭转移历程中,关于EMT发生的分子调控机制研究已取得了良好的进展,但其详细机制仍然不是十分清楚。本文主要介绍生长因子、转录因子、miRNAs、甲基化及其他调控因子在肿瘤EMT中的调控功能,进一步综述EMT在肿瘤侵袭转移中的作用。 相似文献