细胞自噬及其在鼻咽癌中的作用

自噬作为一个重要的自我平衡的细胞回收机制,现逐渐发现在新陈代谢和治疗应激中起了关键作用。它通过消除细胞内过多不必要的蛋白质及受损或衰老的细胞器成分来维持/恢复新陈代谢的稳定。在代谢应激的情况下,自噬被激活。在癌细胞中自噬有两个方面的作用:肿瘤促进作用和肿瘤抑制作用。有功能的自噬可防止会导致遗传不稳定性发生的细胞坏死和炎症反应。另一方面,自噬通过不利代谢环境的循环机制提供能量对肿瘤进程起了重要作用。最近,许多研究表明,自噬在鼻咽癌的治疗中起了重要作用。本文将对自噬所依赖的信号转导途经、自噬与肿瘤的关系、自噬在鼻咽癌治疗中的作用进行综述,以便对自噬功能有个全面的理解。     

自噬在血液肿瘤中的研究进展

<正>自噬是细胞内利用溶酶体内水解酶作用对胞质内容物进行降解,以实现细胞本身代谢所需的能量和某些细胞器更新的过程。自噬不仅可以使细胞在缺乏营养及其他恶性条件下维持生存,而且和很多疾病相关,例如神经退行性变,心脏疾病和肿瘤。通过对自噬作用的研究,可进一步揭示肿瘤发生、发展的潜在机制,为预防和治疗提供了新的靶点。1自噬的生物学过程根据胞质内容物进入溶酶体的方式不同,自噬分为三     

自噬在肿瘤中作用的分子机制研究进展

自噬在饥饿时被诱导以捕获和降解胞内的蛋白质和细胞器,该过程使细胞内组分再循环以维持其代谢和生存需求。自噬也通过控制蛋白质和细胞器的数量和质量维持自身稳态。自噬功能失调导致许多疾病。在肿瘤形成增殖过程中自噬的作用是由多种因素共同决定。自噬在肿瘤中的作用可能是中立的,也可能是抑制肿瘤或者促进肿瘤生长。本文旨在对自噬在肿瘤形成生长中作用机制进行阐述总结,为肿瘤新治疗靶点研发提供线索。     

自噬调控多功能蛋白p62/SQSTM1参与肿瘤及其微环境的研究进展

自噬是细胞内高度保守循环利用细胞代谢产物及陈旧细胞器的降解途径。自噬参与肿瘤的发生、发展及转移,甚至决定肿瘤预后。多功能蛋白p62/SQSTM1不仅作为重要的自噬接头蛋白参与降解过程,还是多个关键信号通路的调控枢纽,在肿瘤及其微环境中发挥了重要作用。本文综述p62/SQSTM1的结构功能及其作用机制的研究进展,旨在为利用自噬调节剂治疗肿瘤寻找关键突破点提供新的理论基础。     

自噬与肾小球疾病关系的研究进展

<正>自噬是真核细胞内降解受损细胞器和大分子蛋白质的生理过程。在生理条件下,它可以通过降解细胞器等物质来维持细胞内稳态;相反,在氧化应激等病理条件下自噬活动的变化既可能延缓疾病进展也可能加速疾病进展。近年来越来越多的研究发现自噬参与肾小球疾病的病理生理过程,自噬可能成为肾小球疾病治疗的靶点,本文就自噬与肾小球疾病关系的进展作一综述。     

自噬与脂肪异位沉积

自噬(autophagy)是细胞依赖溶酶体降解受损的细胞器及大分子物质过程。非脂肪细胞出现脂质沉积时,机体通过脂肪代谢产物、氧化应激、内质网应激等途径激活自噬,降解脂滴以保护非脂肪组织免受脂毒性损害。因此增强自噬可能是治疗2型糖尿病、非酒精性脂肪性肝病、代谢综合征等脂肪异位沉积相关疾病的新途径。本文就自噬与脂肪异位沉积的研究进展进行综述。     

细胞自噬与肿瘤的研究进展

细胞自噬是细胞在某些刺激因素下,细胞内膜性结构包绕损伤的蛋白或细胞器,并通过溶酶体融合降解损伤的蛋白质或细胞器的过程;生理状况下的自噬,对于维持细胞稳态有积极作用;肿瘤形成以后,细胞自噬反为癌细胞提供更多的营养,起到促进肿瘤发展的功能。自噬主要有三种方式,即分子伴侣介导的自噬、微自噬和巨自噬,均通过两个泛素化途径实现。细胞自噬可以通过影响DNA损伤修复、细胞应激反应、肿瘤基因表达、凋亡及病毒感染反应等诸多过程参与细胞癌变,也可能在肿瘤治疗过程中降低了对于化疗和放疗的敏感性,但是在肿瘤进展的不同时期,不同肿瘤之间自噬活性的变化不一。自噬过程中的重要中间产物或关键酶可能成为抗肿瘤药物的靶标,拓展了肿瘤防治思路。     

微小RNA对自噬的调控及其发生机制

自噬是真核细胞中进化上高度保守、用于降解和回收利用细胞内生物大分子和受损细胞器的过程.自噬在细胞应对外界刺激、清除受损物质及细胞生长、分化、死亡中有重要的作用.自噬作为调节机体细胞生长发育和病理生理的重要过程,与多种疾病的发生发展密切相关.研究自噬的发生机制,为开发更多治疗有关疾病的药物提供了理论依据,对疾病的预防和治疗具有重大意义.而微小RNA(miRNA)在多种重要的生命活动过程中扮演着重要角色,对疾病的发生、发展及转归有重要的调节作用.本文介绍一些对自噬有重要调控作用的miRNA,并阐述其在各阶段调控自噬相关基因表达的机制及其对一些疾病的影响.     

自噬调控巨噬细胞参与构建肿瘤微环境研究进展

自噬作为细胞高度保守的胞内代谢产物及衰老、损伤细胞器的降解途径，参与维持细胞稳态。肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）是构成肿瘤微环境的关键细胞，通过极化为M2型促进肿瘤发生、发展及转移。自噬通过调控TAMs极化、代谢来参与肿瘤微环境的构建。本文就自噬调控巨噬细胞与肿瘤微环境相互作用的机制进行阐述，旨在为靶向肿瘤微环境内TAMs和肿瘤细胞自噬调控的治疗提供新的理论基础。     

细胞自噬在血液系统恶性疾病中作用研究进展

细胞自噬是通过溶酶体途径降解细胞自身成分的一种分解代谢过程,该过程异常可使细胞稳态发生变化,影响多种疾病的发生、发展以及治疗。在血液系统恶性疾病中,细胞自噬不仅在造血干细胞的功能维持中起重要作用,还与化疗药物耐药具有相关性。SQSTM1/P62是参与细胞自噬、肿瘤发生的关键蛋白,其水平与细胞自噬调节密切相关。本文就细胞自噬在血液系统恶性疾病发展中的作用及其对化疗疗效影响的研究进展作一综述。     

The role of autophagy in cancer: therapeutic implications

Autophagy is a homeostatic, catabolic degradation process whereby cellular proteins and organelles are engulfed by autophagosomes, digested in lysosomes, and recycled to sustain cellular metabolism. Autophagy has dual roles in cancer, acting as both a tumor suppressor by preventing the accumulation of damaged proteins and organelles and as a mechanism of cell survival that can promote the growth of established tumors. Tumor cells activate autophagy in response to cellular stress and/or increased metabolic demands related to rapid cell proliferation. Autophagy-related stress tolerance can enable cell survival by maintaining energy production that can lead to tumor growth and therapeutic resistance. As shown in preclinical models, inhibition of autophagy restored chemosensitivity and enhanced tumor cell death. These results established autophagy as a therapeutic target and led to multiple early phase clinical trials in humans to evaluate autophagy inhibition using hydroxychloroquine in combination with chemotherapy or targeted agents. Targeting autophagy in cancer will provide new opportunities for drug development, because more potent and specific inhibitors of autophagy are needed. The role of autophagy and its regulation in cancer cells continues to emerge, and studies aim to define optimal strategies to modulate autophagy for therapeutic advantage.     

The role for autophagy in cancer

Autophagy is a survival-promoting pathway that captures, degrades, and recycles intracellular proteins and organelles in lysosomes. Autophagy preserves organelle function, prevents the toxic buildup of cellular waste products, and provides substrates to sustain metabolism in starvation. Although in some contexts autophagy suppresses tumorigenesis, in most contexts autophagy facilitates tumorigenesis. Cancers can upregulate autophagy to survive microenvironmental stress and to increase growth and aggressiveness. Mechanisms by which autophagy promotes cancer include suppressing induction of the p53 tumor suppressor protein and maintaining metabolic function of mitochondria. Efforts to inhibit autophagy to improve cancer therapy have thereby attracted great interest.     

自噬与恶性血液病

自噬是近年来很热门的研究领域,是真核细胞受饥饿、低氧和药物处理等代谢压力下,通过自身降解,获得能量的一种生理过程,研究表明其与恶性血液病的发生发展密切相关.目前关于自噬与恶性血液病之间关系的研究尚存在模糊及矛盾的问题.适宜的治疗方法,应当选择性的抑制肿瘤细胞生长,而同时对正常细胞无损伤.因此在探讨自噬在恶性血液病治疗过程中的作用,如何选择靶向的自噬相关治疗策略亦尤为重要.本文对自噬的发生发展、自噬与恶性血液病的关系以及自噬在恶性血液病中的可能作用机制进行了归纳和总结.     

Autophagy as an antimicrobial strategy

Autophagy is a process of lysosomal degradation that was originally described as a cellular response to adapt to a lack of nutrients and to enable the elimination of damaged organelles. Autophagy is increasingly recognized as a process that is also involved in innate and adaptive immune responses against pathogens. Studies on the regulation of autophagy have uncovered components of the autophagic cascade that can be manipulated pharmacologically. Approaches to modulate autophagy may result in novel strategies for the treatment and prevention of various infections.     

自噬与紫杉醇敏感性

自噬广泛存在于真核生物的病理生理过程中,细胞通过自噬作用维持细胞内合成和分解代谢的平衡,保持内环境稳定。紫杉醇在诱导肿瘤细胞凋亡的同时,也可诱导自噬发生,紫杉醇诱导的自噬可抵抗凋亡,亦可作为凋亡的前提条件或与凋亡协同作用促进肿瘤细胞死亡。调控自噬表达可增加细胞对紫杉醇的敏感性,紫杉醇联合自噬调控治疗有望提高抗肿瘤治疗疗效。     

Targeting autophagy during cancer therapy to improve clinical outcomes

Autophagy is a catabolic process that turns over long-lived proteins and organelles and contributes to cell and organism survival in times of stress. Current cancer therapies including chemotherapy and radiation are known to induce autophagy within tumor cells. This is therefore an attractive process to target during cancer therapy as there are safe, clinically available drugs known to both inhibit and stimulate autophagy. However, there are conflicting positive and negative effects of autophagy and no current consensus on how to manipulate autophagy to improve clinical outcomes. Careful and rigorous evaluation of autophagy with a focus on how to translate laboratory findings into relevant clinical therapies remains an important aspect of improving clinical outcomes in patients with malignant disease.     

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well-conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient-deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.     

mi-RNA调控自噬在癌症中的作用

自噬是通过溶酶体依赖性途径降解和再循环细胞溶质组分或细胞器的保守分解代谢过程,其负责长寿命蛋白质、蛋白质聚集体以及受损细胞器的降解以维持细胞稳态。因此,自噬的异常与许多疾病相关,包括阿尔茨海默病,帕金森病和癌症。根据目前的观点,自噬似乎在癌症形成的早期阶段充当肿瘤抑制剂,但在后期阶段,自噬可以促进肿瘤的生长、扩散。microRNA（miRNA）是内源性非编码小RNA,其通过沉默mRNA靶标来调节基因表达。在体细胞发育、造血、免疫、细胞增殖和死亡以及自噬过程中,miRNA失调表现出巨大的调节潜力。近年来大量的研究表明miRNA可通过调节靶向基因表达来调节细胞自噬进而有助于癌症形成,以及癌症的进展。在本综述中,将简要阐明miRNA对自噬的调控在癌症中的作用。