细胞自噬在肿瘤中的作用

自噬为一种细胞的自我消耗过程,其具有潜在的抗肿瘤生物学活性,亦与肿瘤耐药有关.该文从自噬的调节机制入手,综述自噬参与肿瘤发生的机制,自噬在肿瘤治疗中的作用及应用,以期为自噬在临床上的应用提供依据.     

自噬与凋亡的相互关系在肿瘤方面的研究进展

肿瘤是一类涉及基因、代谢和信号传导异常等多方面因素引起的疾病,其发生的分子机制相当复杂,但本质上仍与细胞增殖与死亡的动态失衡有关。程序性细胞死亡（programmed cell death,PCD）是由基因控制的自杀程序引起的主动性死亡,对于多细胞生物个体发育的正常进行,维持内环境稳态以及抵御外界各种干扰因素方面有着关键性的意义。I型PCD（经典细胞凋亡）和II型PCD（自噬性细胞死亡）调控着肿瘤细胞的增殖与消耗,与肿瘤的发生、发展密切相关。本文结合近年来国内外研究进展,重点就自噬在肿瘤中的作用以及与凋亡的相互关系作一综述。     

自噬与肿瘤

自噬在维持细胞的正常代谢及生存过程中有着重要作用,其在肿瘤的发生机制中也不容忽视,自噬的过程源于自噬小体的形成,包括了诱导、成核、延长、形成完整隔离膜4个步骤。本文就自噬的分子机制、检测方法及其与肿瘤方面的研究进展加以综述。     

调控肿瘤细胞自噬相关分子的研究进展

自噬是真核细胞中的重要生理过程,有助于细胞成分的正常更新。机体处于饥饿状态时,自噬不仅可降解蛋白质产生氨基酸、ATP等,为细胞存活提供条件,还能清除受损的细胞器,维持细胞正常机能。自噬功能的异常与肿瘤的形成发展密切相关,其程度过高或过低均会抑制肿瘤。现已发现自噬受多种分子调控,且作用结果各异。因此,对这些自噬相关分子作用机制的深入研究将成为进一步认识自噬的出发点和治疗肿瘤的突破口。     

自噬调控机制及与肿瘤关系研究进展

自噬是真核细胞通过降解自身的细胞质和细胞器实行“自我消化”的一系列生化过程，它是广泛存在于真核细胞中的生命现象。近年来的研究发现肿瘤的增殖、凋亡信号途径与自噬信号途径相互交错影响，自噬与肿瘤细胞的生存死亡有重要的关系，这预示着自噬将成为肿瘤研究中的一个新热点。     

自噬与肿瘤干细胞

肿瘤干细胞(cancer stem cell,CSC)是一类能持续自我更新并保持分化潜能的细胞,是影响恶性肿瘤形成、增殖、转移、复发的重要因素,并在肿瘤发生发展中起主导作用.研究发现,CSC的生理学功能可受到基因、微环境的影响,除此之外,自噬对维持CSC的存活、分化潜能及维护肿瘤微环境稳定也发挥了重要作用,并且CSC的自噬过程对肿瘤的发生及转移也有重要影响.     

自噬与肿瘤

近期研究发现自噬不仅对细胞内自我平衡调节起着重要作用,而且在肿瘤的发生发展中起着双刃剑的作用。研究自噬的分子机制以及自噬与肿瘤的关系对肿瘤防治有重大意义。     

自噬与肿瘤

近期研究发现自噬不仅对细胞内自我平衡调节起着重要作用,而且在肿瘤的发生发展中起着双刃剑的作用.研究自噬的分子机制以及自噬与肿瘤的关系对肿瘤防治有重大意义.     

自噬在肿瘤中的双重作用

自噬是一种溶酶体降解途径, 通过对细胞内变性蛋白或受损细胞器进行降解, 以维持细胞内物质循环及代谢调节的稳定。自噬是一把双刃剑, 在肿瘤微环境中, 自噬既能在不利环境中提高肿瘤细胞对应激的耐受能力, 维持其生存, 又能在肿瘤发展的不同阶段抑制其产生和转移, 甚至成为某些凋亡缺陷肿瘤细胞的死亡途径。此外, 自噬的双重作用还表现在癌症治疗过程中。因此, 深入探讨自噬在肿瘤中的双重作用有助于为肿瘤防治提供新思路。      

自噬在肿瘤治疗中的作用

自噬是细胞内物质再利用的重要过程,日渐增多的证据表明自噬在肿瘤的发生、发展和抗肿瘤治疗过程中发挥着重要作用。本文就自噬的分子生物学基础及自噬在肿瘤治疗中的作用做一综述。     

Autophagy in tumour cell death

In every moment of a cell's existence one key question is always asked, “To be or not to be”? Cells constantly weigh up signals from their environment against their own integrity and metabolic status and decide whether to live or die. Such cell death decisions are central to the progression and treatment of cancer. The term autophagy describes three processes that deliver cytoplasmic macromolecules and organelles to lysosomes for degradation, the difference between each form being the method of delivery. The most extensively studied form is macroautophagy (hereafter referred to as autophagy) where cytosolic components are engulfed by double membraned autophagosomes. Autophagosomes fuse with lysosomes to form structures called autolysosomes, within which organelles, proteins and other macromolecules are degraded by catabolic enzymes in the acidic lysosome environment. Autophagy, which normally occurs at low levels in unstressed cells, is widely regarded as having a positive effect on cell health as potentially harmful protein aggregates and damaged organelles can be recycled. During periods of nutrient shortage autophagy is enhanced to provide, albeit temporarily, an internal energy source. Autophagy is also enhanced by other stresses encountered by tumour cells and this may protect the cell or aid its demise. In this review we examine the effect of autophagy on cell death decisions in tumour cells.     

自噬及其与结直肠癌的发生和治疗

自噬是细胞通过降解自身的蛋白质及细胞器并循环利用降解产物以维持细胞生存的,过度自噬可导致细胞自噬性死亡.近年来研究发现,自噬在结直肠癌发生、发展及治疗中有重要作用,但其作用机制和对放化疗疗效的影响仍存在争议.     

肿瘤负荷对胃肠道恶性肿瘤患者T1和T2细胞亚群的影响

T淋巴细胞是机体内重要的免疫细胞。1986年Mosmann等根据CD4^＋T细胞分泌细胞因子的不同．首次提出Th细胞分为Th1细胞和Th2细胞。目前,学者们认为Th细胞可分为Th0、Th1、Th2和Th3等4个亚群,Th1亚群主要分泌IL-2、IFN-γ和TNF-β,调节细胞免疫应答;Th2亚群主要分泌IL-4、IL-5、IL-6、IL-10和IL-13等,调节体液免疫应答。     

Motion management in gastrointestinal cancers

The presence of tumor and organ motions complicates the planning and delivery of radiotherapy for gastrointestinal cancers. Without proper accounting of the movements, target volume could be under-dosed and the nearby normal critical organs could be over-dosed. This situation is further exacerbated by the close proximity of abdominal tumors to many normal organs at risk (OARs). A number of strategies have been developed to deal with tumor and organ motions in radiotherapy. This article presents a review of the techniques used in the evaluation, quantification, and management of tumor and organ motions for radiotherapy of gastrointestinal cancers.     

Autophagy Involvement in Olanzapine-Mediated Cytotoxic Effects in Human Glioma Cells

The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy inglioma cells in vitro and in vivo. The proliferation of both LN229 and T98 glioma cells, measured by MTT assay,was suppressed in a concentration-dependent and time-dependent manner. Moreover, apoptosis of both cellswas significantly increased with the treatment of olanzapine as evidenced by increased Bcl-2 expression, Hoechst33258 staining and annexinV-FITC/PI staining. Olanzapine treatment also enhanced activation of autophagy withincreased expression of LC3-II, expression of protein p62, a substrate of autophagy, being decreased. The growthinhibition by olanzapine in both glioma cell lines could be blocked by co-treatment with 3-MA, an autophagyinhibitor. Furthermore, olanzapine effectively blocked the growth of subcutaneous xenografts of LN229 gliomacells in vivo. The increased level of protein LC3-II and decreased level of p62 followed by a decreased level ofBcl-2, suggesting that autophagy may contribute to apoptosis. In addition, reduced proliferation of glioma cellswas shown by a decrease of Ki-67 staining and increased caspase-3 staining indicative of apoptosis in mousexenografts. These results indicated that olanzapine inhibited the growth of glioma cells accompanied by inductionof autophagy and apoptosis both in vitro and in vivo. Olanzapine-induced autophagy plays a tumor-suppressingrole in glioma cells.     

Use of liquid biopsies in gastrointestinal cancers

The use of liquid biopsies is a relatively new tool in diagnosis and management of gastrointestinal cancers and is actively being investigated. Liquid biopsies have become extremely popular in cholangiocarcinoma and pancreatic cancer research. With more prospective trials using this tool for early diagnosis, liquid biopsies may become an important part of cancer management.     

Thrombocytosis as a prognostic marker in gastrointestinal cancers

Thrombocytosis is an adverse prognostic factor in many types of cancer. These include breast cancer, ovarian and other gynecologic cancers, renal cell carcinoma and lung cancers. In gastrointestinal cancers of various locations and histologic types, thrombocytosis has been reported in general to be associated with adverse clinical outcomes. Platelet count measurement is well standardized and available in every clinical laboratory, making its use as a prognostic marker practical. This paper will discuss the data on the prognostic value of thrombocytosis in gastrointestinal cancers as well as pathogenic aspects of the association that strengthen the case for its use in clinical prognostication.     

Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

Objective: To investigate the effects of gambogic acid (GA) on the growth of human malignant glioma cells.Methods: U251MG and U87MG human glioma cell lines were treated with GA and growth and proliferationwere investigated by MTT and colony formation assays. Cell apoptosis was analyzed by annexin V FITC/PI flowcytometry, mitochondrial membrane potential assays and DAPI nuclear staining. Monodansylcadaverine (MDC)staining and GFP-LC3 localisation were used to detect autophagy. Western blotting was used to investigate themolecular changes that occurred in the course of GA treatment. Results: GA treatment significantly suppressedcell proliferation and colony formation, induced apoptosis in U251 and U87MG glioblastoma cells in a timeanddose-dependent manner. GA treatment also lead to the accumulation of monodansylcadaverine (MDC)in autophagic vacuoles, upregulated expressions of Atg5, Beclin 1 and LC3-II, and the increase of punctatefluorescent signals in glioblastoma cells pre-transfected with GFP-tagged LC3 plasmid. After the combinationtreatment of autophagy inhitors and GA, GA mediated growth inhibition and apoptotic cell death was furtherpotentiated. Conclusion: Our results suggested that autophagic responses play roles as a self-protective mechanismin GA-treated glioblastoma cells, and autophagy inhibition could be a novel adjunctive strategy for enhancingchemotherapeutic effect of GA as an anti-malignant glioma agent.     

紧密连接蛋白Claudins与胃肠道肿瘤

Claudins是一种表达于上皮细胞和内皮细胞的紧密连接蛋白,研究发现其异常表达与胃肠道肿瘤的发生及转移有关.Claudim对胃肠道肿瘤的诊断、治疗及预后评估有着广阔的应用前景.     

The latest advances in chemotherapy for gastrointestinal cancers

During the past decade, there has been much progress in various nonsurgical treatments for gastrointestinal malignancies. Endoscopic mucosal resection (EMR) has been widely used as a standard treatment for early gastrointestinal cancers in Japan. For esophageal cancer, definitive chemoradiotherapy with or without EMR has shown the possibility of results comparable with those of surgery in stage I-III disease and is being evaluated in Japan Clinical Oncology Group (JCOG) studies. Definitive chemoradiotherapy with curative intent for locally advanced (T4/M1a) diseases has had a 5-year survival of 17%. In gastric cancers, although no standard regimen has been established yet, recently developed new agents have achieved higher response rates than before. To establish a new standard, various randomized trials including these new agents are now underway. There has been obvious progress in chemotherapy for colorectal cancer. Newly developed agents such as irinotecan and oxaliplatin have provided significant survival prolongation for metastatic colorectal cancer in randomized trials. In other gastrointestinal malignancies, nonsurgical treatments, including eradication of Helicobacter pylori, chemotherapy, and radiotherapy for primary gastric lymphoma are being evaluated in prospective studies. A new molecular targeting agent, imatinib, has provided significant impact in the treatment of gastrointestinal stromal tumor. To provide these advantages to patients, many more gastrointestinal oncologists are urgently needed in Japan.Presentation made at the ASCO-JSCO Joint Symposium held at Tokyo, Japan, on October 18, 2002.