环状RNA在消化系统肿瘤中的研究进展

环状RNA(circular RNA, circRNA)是一类广泛表达于各种真核细胞,具有高度稳定性、保守性和特异性的内源性闭合环状非编码RNA.研究揭示, circRNA与心血管系统疾病、神经系统疾病、肿瘤等众多疾病的发生、发展过程密切相关.越来越多的研究表明, circRNA在消化系统肿瘤的诊断、治疗中有着巨大的潜能,有望成为该类疾病诊断的生物标志物和治疗药物研发的新靶点,而这一方向已成为当前研究者们关注的热点.在消化系统肿瘤的病理衍变过程中, circRNA主要以微小RNA"海绵"的形式发挥调控作用.本文简单介绍了circRNA的生物学功能,详细综述了circRNA在消化系统肿瘤中的研究进展,展望了未来circRNA成为消化系统肿瘤预防、诊断和治疗新靶点的潜力.     

环状RNA及其对肿瘤作用的研究进展

环状RNA(circ RNA)是一类非编码RNA,广泛存在于生物体中,具有结构稳定、半衰期长、高度保守性及特异性表达等生物学特性。circ RNA具有充当mi RNA海绵、调控基因转录、参与蛋白质翻译等功能。circ RNA在乳腺癌、肺癌、结直肠癌、食管癌等肿瘤中均有表达,且与肿瘤的发生发展以及预后密切相关,未来circ RNA在肿瘤早筛查、肿瘤治疗等领域具有巨大潜力。     

环状RNA在呼吸系统疾病中的研究进展

环状RNA(circRNA)作为新型内源性非编码RNA,在高度分化的真核生物中基因广泛表达,通过反向剪接形成共价闭环结构,具有高度稳定性和组织特异性。近些年,随着高通量测序技术和生物信息学的发展,circRNA被大量发现并逐渐成为RNA领域的研究热点。目前已有研究证明circRNA与慢性阻塞性肺疾病、肺动脉高压、肺癌等...     

环状RNA在血管疾病中的研究进展

环状RNA(circRNA)是一类重要的调控性非编码RNA,其含量丰富、性质稳定、存在广泛,并且可以通过多种机制调控基因表达,在血管疾病的发生发展中发挥重要调控作用。文章综述了circRNA在多种血管疾病中的研究现状,以期为相关领域的研究人员提供参考。     

环状RNA在血管钙化中的研究进展

血管钙化（VC）是高血压病、动脉粥样硬化性疾病、肾功能不全和衰老等普遍存在的共同的血管病理表现,由其引起的高病死率和致残率严重影响人们的生活质量。目前,VC的发生发展的分子机制尚不清楚,并且临床上缺乏有效的预防及治疗手段。近年来,越来越多研究表明环状 RNA（CircRNAs）参与疾病发生发展的病理过程,并成为目前的研究热点。同样,大量的研究认为CircRNAs 在 VC 的发生发展过程中也扮演着非常重要的作用。本文就 CircRNAs在血管钙化中的最新研究进展进行综述 。     

环状RNA与心血管疾病研究进展

环状RNA是一类稳定且广泛存在于真核细胞生物中的闭合环状RNA。环状RNA与动脉粥样硬化、心肌病、心力衰竭、心脏衰老等有关。深入研究环状RNA的功能及作用机制可以为预防、诊断、治疗心血管疾病提供新思路。     

环状RNA在肿瘤发生发展过程中的作用

<正>环状RNA(circular RNA)在真核细胞基因表达过程中起到重要的调控作用[1～3]。最近的研究表明,circRNA在肿瘤的发生、进展和治疗抵抗过程中同样发挥着重要的基因调控功能[4～6],可以作为肿瘤抑制剂或加速器发挥作用[5]。随着高通量测序技术的发展,已经可以很容易的比较circRNA在肿瘤组织和癌旁组织中表达水平的差异。截至目前,已经发现数千个在肿瘤组织表达水平明显变化的circRNA[7]。与线性RNA不同,circRN     

环状RNA在食管癌诊断和预后中的研究进展

环状RNA(circular RNA,circRNA)是一种新型内源性环状结构的非编码RNA,受顺式调控元件和相关蛋白反式调控,经“反向剪接”机制产生。circRNA在基因剪接、转录、染色质修饰、miRNA海绵作用及蛋白捕获等方面发挥重要作用。circRNA高度稳定,且在不同组织中差异表达。circRNA异常表达与肿瘤发生和转移相关。然而,食管癌中具有重要功能的circRNA及作用机制目前尚不清楚。本文结合circRNA的功能特点,对circRNA在食管癌发生发展中的作用及其作为食管癌诊断、预后分子标志物的研究进展做一综述。     

肿瘤微环境在食管癌中的研究进展

食管癌(esophageal cancer, EC)是常见的消化系统恶性肿瘤,起病隐匿、侵袭性强,多数患者治疗效果欠佳。肿瘤微环境(tumor microenvironment, TME)是肿瘤细胞生存的局部环境,参与肿瘤细胞增殖、转移和免疫逃逸等重要生物学过程。TME可通过与肿瘤细胞及其细胞因子等协同作用,调控EC的发生发展及治疗。本文就EC微环境的组成,以及靶向TME治疗EC的最新进展进行综述,以期为EC预防和诊疗提供新思路和理论依据。     

肺癌转移的炎症微环境机制研究进展

近年来,炎症微环境在肿瘤进展过程中的作用日益受到重视,多项研究表明肺癌的炎症微环境在肺癌的转移中起着重要作用.炎症微环境可以通过直接或间接促进肿瘤血管生成、细胞增殖和抑制细胞凋亡进程,从而促进肺癌的转移,而这一过程主要是借助炎症因子、炎症信号通路等途径而实现的.本文就近年来肺癌转移的炎症微环境机制相关的研究进展作一综述.     

肿瘤与宿主间的微环境研究进展

宿主局部的微环境在肿瘤的发生、发展和转移的全过程中都起到了积极的参与作用.肿瘤细胞与间质之间通过酶和细胞因子的交换改变了细胞外基质,导致肿瘤细胞侵袭,刺激其播散,促进其生存增殖.因此,一种基于对肿瘤与宿主间的微环境病理学改变的研究而产生的靶向治疗方法将成为未来肿瘤治疗的重要手段.     

Reliability of a single-region sample to evaluate tumor immune microenvironment in hepatocellular carcinoma

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Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma: Relation to the immune cycle

BACKGROUNDVarious histological types of gastric carcinomas (GCs) differ in terms of their pathogenesis and their preexisting background, both of which could impact the tumor immune microenvironment (TIME). However, the current understanding of the immune contexture of GC is far from complete.AIMTo clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept.METHODSIn total, 50 GC cases were examined (15 cases of diffuse GC, 31 patients with intestinal-type GC and 4 cases of mucinous GC). The immunophenotype of GC was assessed and classified as immune desert (ID), immune excluded (IE) or inflamed (Inf) according to CD8+ cell count and spatial pattern. In addition, CD68+ and CD163+ macrophages and programmed death-ligand 1 (PD-L1) expression were estimated.RESULTSWe found that GCs with different histological differentiation demonstrated distinct immune contexture. Most intestinal-type GCs had inflamed TIMEs rich in both CD8+ cells and macrophages. In contrast, more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+ lymphocytes but abundant CD68+ macrophages, while mucinous GC had an IE-TIME with a prevalence of CD68+ macrophages and CD8+ lymphocytes in the peritumor stroma. PD-L1 expression prevailed mostly in intestinal-type Inf-GC, with numerous CD163+ cells observed. Therefore, GCs of different histological patterns have specific mechanisms of immune escape. While intestinal-type GC was more often related to PD-L1 expression, diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters.CONCLUSIONThese data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.     

肺癌微环境中免疫细胞与肿瘤免疫逃逸相关研究进展

肺癌肿瘤局部浸润的免疫细胞、间质细胞及所分泌的活性介质等与肺癌细胞共同构成的局部内环境又被称之为肺癌微环境。肺癌微环境中浸润的免疫细胞参与了肺癌的疾病进展和免疫逃逸。本文对这一群细胞的浸润特征、功能和相互关系进行阐述,探讨其在肺癌发生发展过程中的作用。     

Functions of the CXC ligand family in the pancreatic tumor microenvironment

Therapeutic resistance is the major contributor to the poor prognosis of and low survival from pancreatic cancer (PC). Cancer progression is a complex process reliant on interactions between the tumor and the tumor microenvironment (TME). Members of the CXCL family of chemokines are present in the pancreatic TME and seem to play a vital role in regulating PC progression. As pancreatic tumors interact with the TME and with PC stem cells (CSCs), determining the roles of specific members of the CXCL family is vital to the development of improved therapies. This review highlights the roles of selected CXCLs in the interactions between pancreatic tumor and its stroma, and in CSC phenotypes, which can be used to identify potential treatment targets.     

An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome

Objective

The classical Hodgkin lymphoma (cHL) tumor microenvironment shows an ongoing inflammatory response consisting of varying degrees of infiltrating eosinophils, mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.

Methods

Tumor‐infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.

Results

The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9‐year follow‐up) in age‐adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05‐3‐15). Epstein‐Barr virus (EBV)‐positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.

Conclusions

Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.     

Progressive tumor growth-associated altered tumor microenvironment: implications in a tumor stage-dependent modulation in survival of a murine T cell lymphoma

In the present study using a transplantable murine T cell lymphoma designated as Dalton’s lymphoma, we investigated the role of oxygen, glucose and other environmental factors in evolution of altered survival responses in tumor cells during the late tumor-bearing stages. Tumor progression was observed to be associated with an improvement in the survival ability of tumor cells. Moreover, tumor serum and ascitic fluid obtained from the late tumor bearing stage was found to augment tumor cell survival in vitro, indicating that these humoral components of tumor bearing host contain factors capable of modulating tumor survival. Progressive tumor growth was also shown to be associated with depletion in glucose and oxygen content in the fluids of tumor microenvironment along with a concomitant augmentation in the production of lactate and lactate dehydrogenase. Moreover, tumor cells expressed higher amount of mRNA for inducible nitric oxide synthase, Hypoxia inducible factor-1 and 2 and Hsp70 and VEGF proteins during the late tumor bearing stages. Splenic macrophages and non-adherent splenic lymphocytes from tumor-bearing mice showed an increased production of IL-6, TGF-β, IFN-γ, IL-2R and VEGF during the late tumor-bearing stage, which could be implicated in the differential regulation of tumor growth in a tumor stage dependent manner. In conclusion, the observations of the present study suggest that factors contained in altered tumor microenvironment may act in concert to cause behavioral alterations in tumor cells, with respect to survival, during the course of the progression of a nonsolid T cell lymphoma.     

肥大细胞在肺癌微环境中的研究进展

肺癌是癌症相关疾病的主要死亡原因.肥大细胞是主要的免疫细胞,因其有较长的生存期,参与过敏、寄生虫感染、损伤修复等相关疾病的发生和发展及炎症反应过程,近来研究发现肥大细胞与肿瘤的发展和转归密切相关.对肥大细胞的深入了解能为肺癌的发病机制、预防、治疗等生理病理过程提供有价值的参考和借签.