间充质干细胞源性外泌体及其在肿瘤治疗中的研究进展

外泌体（exosomes）是细胞内多囊泡体（multivesicular bodies,MVBs）与细胞膜融合后释放到细胞外直径为40~100nm的囊泡样小体。作为一种重要的细胞间信息传递分子及遗传物质传递载体,外泌体内含有蛋白质、RNA等多种活性物质,广泛分布于血液、尿液等体液中。目前发现多种类型细胞均可产生外泌体,尤其是间充质干细胞（MSCs）被认为是产生外泌体能力最强的细胞,并且MSCs源性外泌体（MSC-exosomes）与MSCs同样具有向炎症组织及肿瘤组织迁移的特性,为肿瘤治疗提供了一种新思路。由此,本文将从MSC-exosomes生物学特性、分离鉴定方法、肿瘤治疗潜能三方面进行综述。     

白血病微环境中外泌体的研究进展

外泌体是由多种活细胞分泌的广泛分布于多种体液中的微囊泡结构,携带有亲本细胞来源的核酸、蛋白质和脂质等生物信息分子,是细胞间的通讯载体。外泌体在肿瘤进展中起重要作用,参与肿瘤细胞的增殖、迁移、免疫逃逸及血管生成等。在血液系统中,外泌体涉及白血病细胞及周围环境之间的串扰,促进白血病微环境的形成并充当免疫调节剂,是其治疗研究的潜在方向。文章就外泌体的生物学特性及其在白血病肿瘤微环境和免疫调节中的作用进行综述。     

外泌体传输microRNA在肿瘤研究中的进展*

外泌体是一类可以在细胞间传递直径为30～100 nm的内吞衍生囊泡,可包含与其来源和功能相关的蛋白质和RNA 等物质。外泌体作为一种天然的载体,已被视为一种新型的药物传输系统用于肿瘤的治疗。microRNA（miRNA ）是一类新型的RNA调控基因,不仅仅存在于细胞内,亦存在于细胞外,这些细胞外miRNA 可作为分泌型信号分子影响受体细胞表型,并一定程度上反映出供体细胞内的分子改变,具有一定的诊断及潜在的治疗用途。肿瘤患者血液中外泌体高于正常人,并能够包裹肿瘤相关miRNA 行使生物学功能,因此机体通过外泌体传输特异性miRNA 可能在肿瘤的发病过程中扮演着重要的角色。本文将对外泌体作为miRNA 的传输载体在肿瘤发生发展以及肿瘤治疗等方面的研究进行综述。      

外泌体在B细胞肿瘤中的研究进展

外泌体是一种可以携带源细胞多种信息成分,直径30~130 nm的一种生物活性小囊泡。大量研究发现外泌体是由肿瘤细胞或肿瘤微环境细胞分泌的,并通过相互作用影响B细胞肿瘤的增殖、血管生成、耐药和免疫逃逸。同时,外泌体也可作为一种新兴的生物学标志物,用于B细胞肿瘤的诊断和预后判断。另外,外泌体作为天然、无免疫源性的药物载体具有良好的治疗潜能。文章就着重阐述外泌体在B细胞肿瘤诊疗中的研究进展。     

外泌体在多发性骨髓瘤治疗中潜在作用

目的作为细胞间信息的重要传播者,外泌体在肿瘤诊断、治疗和预后等方面起着重要作用。研究证实其相关抑制剂或者类似物等具有抗多发性骨髓瘤(multiple myeloma,MM)的作用。本研究旨在总结国内外研究中外泌体在MM治疗中的潜在作用。方法以"外泌体、多发性骨髓瘤、治疗"为关键词,检索2004-08-2019-01PubMed和万方数据库检索系统中的文献。纳入标准:(1)外泌体的生物学功能;(2)外泌体在MM治疗中作用的研究。经筛选符合要求的文献有49篇。结果MM来源的外泌体某些成分如miRNA、蛋白质、lncRNA等与正常人之间表达存在差异,可利用其抑制剂或类似物发挥抗MM的作用,从而提供潜在治疗靶点。肿瘤来源外泌体及其加工修饰产物可作为一种新的癌症疫苗发挥抗肿瘤免疫;且外泌体的天然纳米结构使其成为药物递送的载体,可用于疾病的治疗。但目前疫苗相关研究较局限,药物载体在肿瘤治疗的应用方面研究亦甚少。结论外泌体可通过特异性表达某些成分而提供潜在治疗靶点,如其本身及其加工产物可制成疫苗,或以运载药物的形式在MM的治疗中发挥潜在作用。但目前这些研究尚处于初级阶段,外泌体应用于MM临床治疗尚需大量研究进一步证实。     

不同细胞来源外泌体对肿瘤微环境的重塑作用

囊泡转运是细胞间沟通的重要方式。随着蛋白质组学、代谢组学、RNA组学等多组学联合研究的发展和进步,研究人员发现外泌体是细胞间通讯的重要信号转导媒介和介质。外泌体携带大量生物活性分子,对细胞生物学功能的发挥具有重要的调控作用,影响肿瘤细胞的特性。越来越多的证据表明,外泌体的功能与其来源的细胞及其内含物成分密切相关。肿瘤来源外泌体以自分泌和旁分泌的方式诱导癌细胞和基质细胞生理功能和代谢状态的改变,基质细胞来源外泌体参与建立、支持和营养肿瘤细胞的肿瘤微环境,并且不同免疫细胞来源外泌体可能呈现截然相反的功能。本文就不同细胞来源外泌体在肿瘤微环境中的作用和机制进行综述,为外泌体在肿瘤诊断、治疗及预后评估中的应用提供参考。     

外泌体在肿瘤转移前微环境形成中的作用

肿瘤的转移前微环境（pre-metastatic niche，PMN）特指原发肿瘤灶为肿瘤细胞远处播散和定植准备的微环境，此微环境的六个特征包括炎症、免疫抑制、血管生成/血管通透性、亲器官性、重编程和淋巴管生成。PMN形成的关键成分包括肿瘤源性分泌因子、细胞外囊泡（含外泌体）、骨髓源性细胞、免疫抑制细胞和宿主基质细胞等，其中，外泌体作为细胞间重要的信使，在肿瘤PMN的形成中具有重要作用。本综述就外泌体在肿瘤PMN形成中的作用进行探讨。     

间充质干细胞来源外泌体在恶性肿瘤中的研究进展

间充质干细胞（mesenchymal stem cells,MSCs）是存在于各种组织中的多能基质细胞。外泌体为细胞间的通讯载体,能在细胞间传递脂质、核酸以及蛋白质等生物活性分子。MSCs分泌的外泌体（mesenchymal stem cell-derived exosomes,MSC-EXO）为肿瘤微环境（tumor microenvironment,TME）的主要组成部分,并且在肿瘤的发生发展、血管生成及转移过程中发挥重要作用。本文旨在对MSCs来源的外泌体在癌症研究及其对肿瘤的作用机制予以综述,为适当利用修饰的MSC-EXO作为肿瘤治疗的策略提供新思路。      

外泌体影响乳腺癌转移机制的研究进展

乳腺癌是女性发病率最高的恶性肿瘤。早期乳腺癌患者中的30%能够检测到循环肿瘤细胞,这是导致约90%乳腺癌患者转移致死的主要原因。外泌体是一系列具有生物功能的小囊泡,携带多种活性成分,不同类型供体细胞来源的外泌体均可影响乳腺癌细胞和基质细胞,在肿瘤微环境中发挥不同的作用,调控乳腺癌的转移。笔者从外泌体影响肿瘤微环境、转移前生态位形成、循环肿瘤细胞在血液和靶器官中存活机制等方面,综述了外泌体在乳腺癌进展和转移中的作用。     

外泌体在癌相关成纤维细胞与肿瘤细胞交互作用中的研究进展

癌相关成纤维细胞（cancer associated fibroblasts, CAF）在肿瘤微环境中起着重要作用,其不仅能影响正常细胞的恶性转化,还促进肿瘤细胞的增殖、侵袭及远处转移。CAF通过物理吸引作用促进癌细胞转移、促进肿瘤血管生成,影响肿瘤细胞的代谢,从而促进恶性侵袭。外泌体在微环境中能够从供体细胞向受体细胞传递分子和遗传物质,是分子在细胞间转移的载体,在CAF与恶性肿瘤细胞沟通中发挥重要作用。CAF分泌外泌体促进肿瘤的发展,肿瘤细胞源性外泌体能激活CAF。外泌体具有作为靶向药物递送载体的潜在作用,外泌体作为生物特异性标志物也可用于癌症的早期检测、诊断和预后,具有较好的临床应用前景。     

基于记忆性干性T细胞和中心记忆性T细胞的细胞免疫治疗在血液肿瘤治疗中的价值

近年来,以抗原嵌合受体T细胞(CAR-T)为代表的细胞免疫治疗在血液肿瘤治疗中取得重大突破.记忆性干性T细胞(Tb)和中心记忆性T细胞(TCM)是T细胞免疫治疗强有力的载体,如何在体内及体外调控该类细胞的分化、如何利用其构建强效的治疗系统而避免潜在的毒副作用受到研究者们的关注.文章主要总结了第58届美国血液学会(ASH)年会关于TSCM和TCM在血液肿瘤治疗中的价值和相关研究进展.     

Hematological malignancies: role of miRNAs and their in silico aspects

Hematological malignancies is a broad term that includes blood cell cancers including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), Myelodysplastic syndrome, acute lymphocytic leukemia (ALL), multiple myelomas (MM) and lymphomas. miRNAs are ~22-nt long non-coding RNAs that play a very important role in gene regulation by binding to mRNA at their complementary sequence. These miRNAs are conceptually connected with various signal and pathway networks that make them capable of regulating various diseases including hematological malignancies. These miRNAs are not only playing regulatory roles in hematological malignancies, but are also providing new potent markers for efficient diagnosis and prognosis for hematological malignancies patients. Since the discovery of very first miRNA, the importance and role of miRNAs have been established in various fields, and there is a need to search for new potent miRNAs and their targets. A large amount of sequence data have been generated in last few years, which has further generated the need to develop efficient and reliable computational tools to analyze and extract out relevant information promptly from raw data. Here, we review various possible roles played by miRNA in hematological malignancies, principles involved in miRNA gene identification, target prediction and their preceding role in hematological malignancies research.     

Prognostic Impact of Adiposity in Hematological Malignancies: A Systematic Review and Meta-analysis

It has been proposed that direct measurement of adiposity has a greater accuracy as a prognostic factor in various malignancies than anthropometric measures such as BMI. We evaluated the association of visceral and subcutaneous adiposity with outcomes in patients with hematological malignancies with a systematic review and meta-analysis. This systematic review included patients with hematological malignancies who had the analysis of overall mortality and progression-free survival according to their adiposity status. We identified 3137 articles, of which we included seven studies. Patients with visceral low visceral adiposity had 2 times greater mortality risk (HR 2.02, P = .0004) and 80% higher risk of death or disease progression (HR 2.98, P = 0.0002), than patients with normal visceral obesity. Patients classified with subcutaneous adipopenia had almost 3 times greater mortality risk. In conclusion, hematological malignancy patients having low adiposity (subcutaneous or visceral) have worse outcomes.     

Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies

Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized.     

吲哚胺-2 3-双加氧酶对血液系统肿瘤治疗与预后的意义

肿瘤免疫反应作为一种保护机制,在血液系统肿瘤形成时即自发产生。然而,在临床明确诊断肿瘤之前,活化的免疫细胞和效应细胞因子的存在已经引发多种免疫抑制途径,这些途径相互协同并导致肿瘤抗原特异性T细胞的功能障碍,最终使血液系统肿瘤处于耐受状态。吲哚胺-2,3-双加氧酶（indoleamine 2,3-dioxygenase,IDO）为上述免疫抑制途径的重要成员之一,IDO通过代谢色氨酸,引起反馈性调节,从而限制炎症反应和引起T细胞获得性耐受,最终抑制肿瘤免疫反应。IDO免疫抑制的作用使得IDO抑制剂成为治疗多种肿瘤的重要免疫治疗方法,特别是在血液系统肿瘤中的作用为近些年的研究热点。本文就IDO及其抑制剂在血液系统肿瘤中的治疗作用和预后意义进行综述。      

HIV-Related Hematological Malignancies: A Concise Review

HIV (Human Immunodeficiency Virus) and its consequence, AIDS (acquired immunodeficiency syndrome) are responsible for a human tragedy of incalculable proportions. Patients afflicted by it are susceptible due to an early senescence of the immune system to opportunistic infections and malignancies. Since the introduction in 1996 of highly active anti-retroviral therapy (HAART), the landscape of malignancies associated to HIV/AIDS has changed in a significant manner as a direct result of significant improvement in the morbidity, mortality and life expectancy of HIV infected patients. While there has been a significant decrease in developed countries of malignancies such as Kaposi's sarcoma and Primary CNS lymphomas associated to the pre-HAART HIV-related immunodeficiency, hematological malignancies, particularly non-Hodgkin lymphomas continue to be the most common cancer-related cause of death in HIV infected individuals. This concise review of the subject highlights aspects of the natural history of HIV disease as it relates to the cause of malignancies with emphasis in the management and treatment of HIV-related hematological malignancies.     

BCL-2抑制剂在血液恶性肿瘤中的靶向治疗应用及作用机制

细胞凋亡受到抑制是血液恶性肿瘤细胞的突出特征。B细胞淋巴瘤-2(B-cell lymphoma-2,BCL-2)是细胞凋亡关键性蛋白调节因子,在多种血液恶性肿瘤中有不同程度的表达。高表达BCL-2的肿瘤细胞抗细胞凋亡能力显著增强,靶向抑制BCL-2成为抗血液肿瘤的研究热点之一。维奈克拉是首个获批上市的BCL-2抑制剂(BCL-2 inhibitor, BCL-2i),用于慢性淋巴细胞白血病、急性髓系白血病及骨髓增生异常综合征的治疗。研究表明维奈克拉对其他血液恶性肿瘤如B细胞非霍奇金淋巴瘤及多发性骨髓瘤也具有抗肿瘤活性。本文就BCL-2抗凋亡机制、BCL-2i在血液恶性肿瘤中的临床应用以及BCL-2i耐药的可能机制作一简要综述。     

82例血液恶性肿瘤合并静脉血栓栓塞症患者的临床特点分析

目的:探讨血液系统肿瘤患者合并静脉血栓栓塞症(venous thromboembolism,VTE)的临床特点.方法:回顾性分析2012年1月至2020年12月宁夏医科大学总医院收治的82例血液肿瘤合并VTE患者的住院资料并作为病例组,以同期100例未合并VTE的血液肿瘤患者为对照组.结果:血液肿瘤并发VTE以急性白血...