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[肿瘤干细胞研究——诊断与治疗的基础及挑战]

[Tumor stem cell research - basis and challenge for diagnosis and therapy].

作者信息

Karlic Heidrun, Herrmann Harald, Schulenburg Axel, Grunt Thomas W, Laffer Sylvia, Mirkina Irina, Hubmann Rainer, Shehata Medhat, Marian Brigitte, Selzer Edgar, Pfeilstöcker Michael, Pittermann Elisabeth, Jäger Ulrich, Pehamberger Hubert, Zielinski Christoph, Valent Peter

机构信息

Ludwig Boltzmann Cluster Oncology (LBI for Leukemia Research), Hanusch Hospital, Vienna, Austria.

出版信息

Wien Klin Wochenschr. 2010 Jul;122(13-14):423-36. doi: 10.1007/s00508-010-1408-z. Epub 2010 Jul 22.

DOI:10.1007/s00508-010-1408-z
PMID:20645015
Abstract

Biological features of tumor cells relevant to progression, metastasis, and prognosis in cancer patients have been investigated for many years. During the past few years, the concept of tumor stem cells has gained widespread acceptance. The cancer stem cell (CSC) model is based on the observation that continuous growth of tumors depends on a small population of immature neoplastic cells with unlimited proliferative potential. In contrast to these CSC, more mature clonal cells in the same neoplasm undergo apoptosis and die after a variable number of cell divisions. The self-renewal capacity of CSC plays a central role in this scenario and enables permanent tumor cell repopulation in vivo in patients as well as in experimental animals, e.g., immunodeficient mice. Based on the stem cell concept, it is clear that the success of an anti-neoplastic approach depends on efficient targeting and elimination of CSC. An important aspect of CSC is their intrinsic resistance against conventional drugs. Therefore, a major focus in current research is molecular targets and their expression in CSC, with the goal to use targeted drugs for CSC elimination. It is the hope for the future that therapeutic approaches involving CSC-targeting concepts will lead to sustained remission and thus improvement of prognosis in leukemia and cancer patients.

摘要

多年来,人们一直在研究肿瘤细胞与癌症患者病情进展、转移及预后相关的生物学特性。在过去几年中,肿瘤干细胞的概念已被广泛接受。癌症干细胞(CSC)模型基于这样的观察结果:肿瘤的持续生长依赖于一小部分具有无限增殖潜能的未成熟肿瘤细胞。与这些CSC相反,同一肿瘤中更成熟的克隆细胞在经历不同次数的细胞分裂后会发生凋亡并死亡。CSC的自我更新能力在这种情况下起着核心作用,并能使患者体内以及实验动物(如免疫缺陷小鼠)体内的肿瘤细胞永久重新增殖。基于干细胞概念,很明显抗肿瘤方法的成功取决于对CSC的有效靶向和清除。CSC的一个重要方面是它们对传统药物的内在抗性。因此,当前研究的一个主要重点是分子靶点及其在CSC中的表达,目标是使用靶向药物清除CSC。未来的希望是,涉及CSC靶向概念的治疗方法将导致持续缓解,从而改善白血病和癌症患者的预后。

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[Tumor stem cell research - basis and challenge for diagnosis and therapy].[肿瘤干细胞研究——诊断与治疗的基础及挑战]
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2
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Emerging functional markers for cancer stem cell-based therapies: Understanding signaling networks for targeting metastasis.基于癌症干细胞的治疗方法的新兴功能标志物:了解用于靶向转移的信号网络。
Semin Cancer Biol. 2018 Dec;53:90-109. doi: 10.1016/j.semcancer.2018.06.006. Epub 2018 Jun 30.
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At the crossroads of cancer stem cells and targeted therapy resistance.处于癌症干细胞与靶向治疗耐药性的交叉点。
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Alternative splice variants of DCLK1 mark cancer stem cells, promote self-renewal and drug-resistance, and can be targeted to inhibit tumorigenesis in kidney cancer.DCLK1 的可变剪接异构体标记癌症干细胞,促进自我更新和耐药性,并可作为靶点抑制肾癌的肿瘤发生。
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Insights into new mechanisms and models of cancer stem cell multidrug resistance.癌症干细胞多药耐药性新机制和新模型的研究进展。
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Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance.靶向癌症干细胞特异性标志物和/或相关信号通路以克服癌症耐药性。
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Smad inhibitor induces CSC differentiation for effective chemosensitization in cyclin D1- and TGF-β/Smad-regulated liver cancer stem cell-like cells.Smad抑制剂诱导细胞周期蛋白D1和转化生长因子-β/ Smad调控的肝癌干细胞样细胞中的癌症干细胞分化,以实现有效的化学增敏作用。
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Stem cell programs in cancer initiation, progression, and therapy resistance.肿瘤起始、进展和治疗抵抗中的干细胞程序。
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Cancer stem cell (CSC) resistance drivers.癌症干细胞(CSC)耐药性驱动因素。
Life Sci. 2019 Oct 1;234:116781. doi: 10.1016/j.lfs.2019.116781. Epub 2019 Aug 17.

引用本文的文献

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Ludwig Boltzmann Cluster Oncology (LBC ONC): first 10 years and future perspectives.路德维希·玻尔兹曼集群肿瘤学(LBC ONC):首个十年及未来展望。
Wien Klin Wochenschr. 2018 Sep;130(17-18):517-529. doi: 10.1007/s00508-018-1355-7. Epub 2018 Jul 13.
2
[Cancer stem cells as the therapeutic target of tomorrow].[癌症干细胞作为未来的治疗靶点]
Wien Med Wochenschr. 2017 Feb;167(1-2):25-30. doi: 10.1007/s10354-016-0446-1. Epub 2016 Mar 4.
3
Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models.

本文引用的文献

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Phosphoinositide signalling in cancer: beyond PI3K and PTEN.癌症中的磷酸肌醇信号转导:超越 PI3K 和 PTEN。
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Stem cell divisions controlled by the proto-oncogene BMI-1.由原癌基因BMI-1控制的干细胞分裂。
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5
Nonredundant roles for Runx1 alternative promoters reflect their activity at discrete stages of developmental hematopoiesis.Runx1 替代启动子的非冗余作用反映了它们在发育性造血的不同阶段的活性。
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