肿瘤休眠研究现状

肿瘤休眠(tumor dormancy)临床上常见于原发肿瘤行根治性切除后,患者体内存在微小瘤灶或微量肿瘤细胞,在一定时间范围内既没有被机体清除,也没有增殖生长,但这些肿瘤细胞仍具有增殖潜能,可在数年乃至数十年后再次增殖,导致肿瘤的复发或远处转移.旨在诱导肿瘤休眠,阻止肿瘤生长,延长患者生存期的肿瘤休眠疗法,逐渐成为肿瘤治疗的新策略.但目前对肿瘤休眠及其机制的研究尚不深入.     

肿瘤休眠研究进展

肿瘤休眠是一个临床概念,已有近50年的研究历史,经历了对肿瘤休眠的现象描述、肿瘤休眠动物模型的建立、肿瘤休眠机制研究、实验性肿瘤休眠诱导与肿瘤休眠疗法等阶段.休眠肿瘤细胞的长期存在是恶性肿瘤难以彻底根治的主要原因,也是导致肿瘤复发和远处转移的根源.彻底阐明肿瘤休眠机制,将有助于实现对肿瘤复发与转移的有效控制.     

肿瘤休眠与复苏的分子调节及临床对策

肿瘤转移实际上是一个低效率的过程.肿瘤休眠的病例在临床也很多见,比如乳腺癌在长期休眠之后才出现转移复发.阐明诱导、维持和终止肿瘤休眠的机制具有重要的临床意义.目前认为,一旦到达新的器官,癌细胞和靶器官之间的分子相互作用可能决定了癌细胞是进入休眠状态还是生长状态.转移生长提供了一个时空广阔的肿瘤治疗靶标.任何能够防止转移生长的治疗都具有临床应用潜能.     

癌瘤转移的生物学(综述)

转移是癌瘤最基本的生物学特性之一。癌瘤患者往往在原发瘤被控制后,由于转移瘤的发生和发展而丧失生命。因此,癌瘤转移的抑制和预防是目前肿瘤研究中的一个重要方面。转移瘤可经血道或淋巴道发生,而这两条途径又互相密切相关。癌瘤从原发瘤转移到远隔部位是一个复杂的过程,一般认为可分为下列四个阶段:①原发瘤释放瘤细胞;②瘤细胞在脉管内转运;③瘤细胞被阻留;④在另一脏器脉管外生长并形成转移灶。转移瘤形成与否     

一种新型肿瘤血管生成抑制因子——血管稳定素的研究进展

为了研究原发性肿瘤抑制其转移瘤生长的分子机制，Ｏ’Ｒｅｉｌｌｙ等从一个原发性肺肿瘤抑制其转移瘤的小鼠模型上，分离纯化到一个由原发瘤产生的抑制肿瘤血管生成和转移瘤生长的多肽，并命名为血管稳定素。     

抑制肿瘤转移的技术

癌症是一种主要的致死性疾患,病人往往死于转移。本文综述肿瘤血运转移过程及其控制技术。转移过程血运转移是一个连续的过程,在概念上可分为四个独立的阶段:1.原发瘤的生长;2.侵入毗邻静脉;3.活瘤细胞释放到血液循环;4.瘤细胞在远位器官滞留和生长。原发瘤原发瘤在形成转移中的重要     

肿瘤休眠与复苏的分子调节及临床对策

肿瘤转移实际上是一个低效率的过程。肿瘤休眠的病例在临床也很多见,比如乳腺癌在长期休眠之后才出现转移复发。阐明诱导、维持和终止肿瘤休眠的机制具有重要的临床意义。目前认为,一旦到达新的器官,癌细胞和靶器官之间的分子相互作用可能决定了癌细胞是进入休眠状态还是生长状态。转移生长提供了一个时空广阔的肿瘤治疗靶标。任何能够防止转移生长的治疗都具有临床应用潜能。     

肿瘤休眠研究进展

肿瘤休眠是一个临床概念，已有近50年的研究历史，经历了对肿瘤休眠的现象描述、肿瘤休眠动物模型的建立、肿瘤休眠机制研究、实验性肿瘤休眠诱导与肿瘤休眠疗法等阶段。休眠肿瘤细胞的长期存在是恶性肿瘤难以彻底根治的主要原因，也是导致肿瘤复发和远处转移的根源。彻底阐明肿瘤休眠机制，将有助于实现对肿瘤复发与转移的有效控制。     

转移瘤所在部位对肿瘤的生长和化疗效果的影响

当前,化疗时人们总是依据肿瘤的原发部位选定药物,尽管决定化疗时肿瘤多半已有不止一处转移。这并不很合理,因为,使用化疗的患者,多已有了远处转移,而且原发瘤可能早已被去除,药物的对象是散居别处的转移瘤。转移瘤的生长,与其说按其原发瘤的特性,勿宁说更多地依赖于转移所在部位的环境影响。Breur(1966)发现从不同部位的原发瘤转至肺的继发瘤以统一的速度增长;相反,原发瘤相同而转移瘤部位不同的继发     

以骨髓转移为首发表现的不明原发部位肿瘤的临床及形态学分析

目的：研究骨髓转移瘤的临床和形态学特点。方法：分析总结21例骨髓转移瘤的临床及形态学资料。结果：临床表现以骨痛、贫血、血小板减少常见,易误诊为多发性骨髓瘤和其他血液病,多数未查到原发肿瘤部位。结论：骨髓穿刺和活检对骨髓转移瘤,特别是原发肿瘤不明确者具有重要的诊断价值。     

Development of the Relationship between Angiogenesis and Tumor Dormancy

Tumor dormancy, a complex and still poorly understood phenomenon, has been defined by the long-term persistence of occult can- cer cells during tumor progression. Recurrence and metastasis may occur just because of an activation of a small portion of the tumor cells. In our view, sustained angiogenesis is considered essential in triggering invasive tumor growth. Here we analyze the correlation between angiogenesis and tumor dormancy, the establishment of tumor dormancy models, the imaging strategies and the new biomarkers for dececting microscopic tumors before or during the angiogenic switch. It imperative to understand the role of an- giogenesis in tumor dormancy, as this will accelerate the development of anti-angiogenesis techniques to induce dormancy and/or eradicate dormant disease.     

肿瘤休眠机制与治疗靶点的发现

肿瘤休眠（tumor dormancy）是指肿瘤细胞在人体内长期存在而没有明显生长的一种状态。肿瘤休眠的现象非常普遍,休眠的肿瘤细胞在部分肿瘤患者甚至正常人体内均可检测到。休眠细胞的长期存在是肿瘤复发和远处转移的根源之一,对肿瘤休眠机制和标志物的深入研究将有助于设计靶向治疗。本文中我们主要就肿瘤休眠发生的机制、肿瘤休眠与肿瘤干细胞的关系进行综述。     

A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis.

Mechanisms that regulate the transition of micrometastases from clinically undetectable and dormant to progressively growing are critically important but poorly understood in cancer biology. Here we examined the effect of a primary tumor on the growth of solitary tumor cells in the mouse liver, as well as on the development of tumor angiogenesis in a dorsal skin-fold chamber. s.c. placement of a CT-26 (BALB/c-derived mouse colon carcinoma) primary tumor markedly inhibited development of liver metastasis in BALB/c mice after subsequent intraportal injection of tumor cells. Dorsal skin-fold chamber experiments showed that this growth inhibition paralleled a strong antiangiogenic effect by the primary tumor. Furthermore, intravital microscopy of the liver after intraportal injection of green fluorescent protein-expressing tumor cells showed that primary tumors promoted dormancy of single tumor cells for up to 7 days. Immunohistological staining for Ki-67 confirmed that these solitary cells were indeed dormant. In contrast, in the absence of a primary tumor, GFP-expressing tumor cells quickly developed into micrometastases. Thus, primary CT-26 tumor implants nearly abrogated tumor metastasis by inhibition of angiogenesis and by promoting a state of single-cell dormancy. Knowledge of the mechanism underlying this dormancy state could result in the development of new therapeutic tools to fight cancer.     

肿瘤休眠及其机制研究进展

肿瘤休眠(tumordormancy)是临床上普遍存在的一种现象,也是恶性肿瘤细胞的生物学特征之一,休眠细胞的长期存在是恶性肿瘤难以彻底根治的主要原因,也是导致肿瘤复发和远处转移的根源之一。本文从临床上发现肿瘤休眠存在、肿瘤休眠概念的演进、肿瘤休眠动物模型的建立、肿瘤休眠的分子及调控机制,以及肿瘤休眠的诱导、维持、再激活等方面进行了综述。旨在为开发诱导肿瘤休眠的药物和应用肿瘤休眠疗法根治肿瘤提供有益的线索。     

Do all roads lead to Rome? Routes to metastasis development

Metastasis, the life-threatening aspect of cancer, is a systemic disease process. Considerable progress has been made in recent years regarding how tumor cells circulating in the blood and lymphatic systems interact with and extravasate into secondary sites, and what determines whether these disseminated tumors cells survive, remain dormant or go on to form macrometastases. New insights into the routes that tumor cells take once leaving the primary tumor have emerged. Novel concepts regarding early seeding of metastases coupled to parallel progression, self-seeding of primary tumors by circulating tumor cells and the induction of premetastatic niches in distant organs by primary tumors have come to the fore. The perceived role of the lymphatic system in determining patterns of metastasis formation in distant organs has been reassessed. Together these new insights have the potential to offer new therapeutic options. In particular, the regulation of tumor cell dormancy emerges as a key event in metastasis formation, and therapeutic control of dormancy holds the promise of rendering cancer a chronic rather than life-threatening disease.     

Current status in human breast cancer micrometastasis

PURPOSE OF REVIEW: Current research and clinical developments on hematogeneous micrometastasis in breast cancer patients are summarized. RECENT FINDINGS: Distant metastasis is the leading cause of cancer-related death in breast cancer and bone marrow is a common homing organ for blood-borne disseminated tumor cells derived from primary breast carcinomas. Sensitive immunocytochemical or molecular assays now allow the detection of single disseminated tumor cells in bone marrow or the peripheral blood at a frequency of 10 and these cells are detected in 10-60% of breast cancer patients without clinical or even histopathologic signs of metastasis. Recently, evidence has emerged that the detection of disseminated tumor cells and circulating tumor cells may provide important prognostic information, and in particular might help to monitor efficacy of therapy. Moreover, the characterization of disseminated tumor cells/circulating tumor cells has shed new light on the complex process underlying early tumor cell dissemination and metastatic progression in cancer patients. SUMMARY: Research on disseminated tumor cells/circulating tumor cells will help to identify novel targets for biological therapies aimed at preventing metastatic relapse and to monitor the efficacy of these therapies. In particular, understanding tumor dormancy and identifying metastatic stem cells might result in the development of new concepts for antimetastatic therapies.     

节律化疗诱导肿瘤休眠的研究进展

肿瘤休眠是恶性肿瘤复发转移的基础,各种微转移病灶及循环中的肿瘤细胞和肿瘤干细胞被认为是休眠状态的肿瘤细胞可能的存在形式。目前认为靶向治疗及内分泌治疗等手段可以诱导肿瘤细胞长期处于休眠状态,抑制肿瘤复发。节律化疗是以小剂量持续给药为特点的化疗方式,可以抑制肿瘤血管生成、恢复宿主抗肿瘤免疫,是一种作用于肿瘤微环境,诱导肿瘤休眠的治疗手段。但因其用药方式、剂量及疗效判定方式尚无统一认识,对肿瘤细胞生物学行为的影响尚未清楚,需要进一步体内、体外实验证实。     

β1-integrin: a potential therapeutic target in the battle against cancer recurrence

Primary cancer treatment, involving both local and often systemic adjuvant therapy, is often successful, especially if the cancer is detected at an early stage of progression. However, for some patients, the cancer may recur either locally or as distant metastases, in some cases many years after apparently successful primary treatment. Significant tumor dormancy has been documented in several cancers, such as breast, melanoma, and renal cancer. Tumor dormancy has long been recognized as an important problem in management of cancer patients. Recent work has clarified biologic aspects of tumor dormancy and has shown that dormant tumor cells may be resistant to cytotoxic chemotherapy and radiation. This work has led to recognition of a key role for β1-integrin in regulating the switch from a dormant state to active proliferation and metastasis. Here we discuss the role of β1-integrin and its signaling partners in regulating the dormant phenotype. We also consider possible therapeutic approaches, such as small molecules or antibodies (ATN-161, volociximab, and JSM6427), directed against β1-integrin signaling to target dormant cancer cells and to prevent metastatic recurrence.     

Metastasis review: from bench to bedside

Cancer is the final result of uninhibited cell growth that involves an enormous group of associated diseases. One major aspect of cancer is when cells attack adjacent components of the body and spread to other organs, named metastasis, which is the major cause of cancer-related mortality. In developing this process, metastatic cells must successfully negotiate a series of complex steps, including dissociation, invasion, intravasation, extravasation, and dormancy regulated by various signaling pathways. In this review, we will focus on the recent studies and collect a comprehensive encyclopedia in molecular basis of metastasis, and then we will discuss some new potential therapeutics which target the metastasis pathways. Understanding the new aspects on molecular mechanisms and signaling pathways controlling tumor cell metastasis is critical for the development of therapeutic strategies for cancer patients that would be valuable for researchers in both fields of molecular and clinical oncology.