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干细胞在头颈癌生物学及治疗中的意义。

Implication of stem cells in the biology and therapy of head and neck cancer.

作者信息

Wollenberg Barbara

机构信息

Klinik für Hals-, Nasen- und Ohrenheilkunde, Medizinische Fakultät Lübeck, Germany.

出版信息

GMS Curr Top Otorhinolaryngol Head Neck Surg. 2011;10:Doc01. doi: 10.3205/cto000074. Epub 2012 Apr 26.

DOI:10.3205/cto000074
PMID:22558051
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3341578/
Abstract

The progress which has been made in the therapy of patients with head and neck cancer in recent years mainly concern the HPV associated HNSCC and the quality of life. The overall survival of patients carrying non HPV associated HNSCC during the last thirty years has not experienced any significant improvement and must be referred to as static [1], [2]. The problem of the illness remains unchanged in the frequent and poorly controllable relapse situation. The locoregionally originating tumours or lymph node metastases show a considerably poorer response towards current therapies. Likewise for a number of patients a formation of distant metastases seems to develop during the course of the illness. Those distant metastases are also therapeutically rather difficult to control. Therefore the mortality of the non HPV induced head and neck cancer remains unchanged. The term "stem cell" describes the entity cell, which acts as a reservoir for new cells in order to replace defective or necrotic cells. A fundamental characteristic of stem cells is the constant ability to multiply into different type of cells, which subsequently do not proliferate. With the insight of new knowledge within the regenerative medicine and the ability of stem cells of self regenerating proliferation and their multipotency in the differentiation, the origin of cancer attains a new distinction. If you look on the tumour as a malignant wound it becomes obvious, that the regeneration or the composition of additional tissue depends on the presence and differentiation of stem cells. The wound healing, which is a regeneration of tissue depends not only on stationary stem cells. In fact stem cells are attracted for "homing" in the defective areas by despatch of various messengers, which then form and replace the vascular tree or other tissue [3], [4].Next to those stem cells, which functionally help to form tumour tissue, a small entity of "real cancer stem cells" in solid tumours is expected. Those occur in tumours and they have typical stem cell characteristics like self-regeneration and the potential of differentiation and are potentially responsible for tumour growth. With their ability of self-regeneration they would have the ability to form a complete tumour out of every single cell. That tumour would histologically look like the tumour those cells initially originated from. Of particular interest regarding those currently still elusive cancer stem cells is their resistance towards current therapies like radiotherapy or chemotherapy. Those insights now get a completely new meaning in tumour biology: Does a cancer stem cell exist, which is able to initiate and keep up tumour growth despite all possible therapeutic interventions? This presentation will outline the current views regarding cancer stem cells in non HPV associated HNSCC and it will highlight problems, which are currently researched on. The objective must be to understand the biology of those cells in a way that make an extended range of therapeutics possible. A therapy, which specifically targets cancer stem cells, could improve the chances of recovery.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/4d57e662333f/CTO-10-01-g-003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/a3f55354b4e0/CTO-10-01-g-001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/a3a638998f78/CTO-10-01-g-002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/4d57e662333f/CTO-10-01-g-003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/a3f55354b4e0/CTO-10-01-g-001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/a3a638998f78/CTO-10-01-g-002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2e4/3341578/4d57e662333f/CTO-10-01-g-003.jpg
摘要

近年来,头颈部癌患者的治疗进展主要涉及与人乳头瘤病毒(HPV)相关的头颈部鳞状细胞癌(HNSCC)以及生活质量。在过去三十年中,携带非HPV相关HNSCC的患者的总体生存率没有显著提高,可说是处于停滞状态[1,2]。在频繁且难以控制的复发情况下,疾病问题依然未变。局部原发肿瘤或淋巴结转移对当前治疗的反应相当差。同样,许多患者在病程中似乎会发生远处转移。这些远处转移在治疗上也相当难以控制。因此,非HPV诱发的头颈部癌的死亡率保持不变。“干细胞”一词描述的是实体细胞,它作为新细胞的储备库,以替代有缺陷或坏死的细胞。干细胞的一个基本特征是持续具有分化为不同类型细胞的能力,而这些分化后的细胞随后不再增殖。随着再生医学新知识的深入以及干细胞自我再生增殖能力及其分化多能性的发现,癌症的起源有了新的认识。如果将肿瘤视为恶性伤口,那么很明显,组织的再生或额外组织的形成取决于干细胞的存在和分化。伤口愈合作为组织的再生,不仅依赖于静止的干细胞。实际上,干细胞通过各种信使的传递被吸引到缺陷区域“归巢”,然后形成并替代血管树或其他组织[3,4]。除了那些在功能上有助于形成肿瘤组织的干细胞外,实体瘤中还存在一小部分“真正的癌症干细胞”。它们存在于肿瘤中,具有自我更新和分化潜能等典型干细胞特征,可能对肿瘤生长负责。凭借其自我更新能力,它们能够从每一个细胞形成一个完整的肿瘤。该肿瘤在组织学上看起来会与那些细胞最初起源的肿瘤相似。关于这些目前仍难以捉摸的癌症干细胞,特别值得关注的是它们对放疗或化疗等当前治疗方法的抗性。这些见解在肿瘤生物学中现在有了全新的意义:是否存在一种癌症干细胞,尽管进行了所有可能的治疗干预,仍能启动并维持肿瘤生长?本报告将概述目前关于非HPV相关HNSCC中癌症干细胞的观点,并突出当前正在研究的问题。目标必须是以一种使更广泛的治疗方法成为可能的方式来理解这些细胞的生物学特性。一种专门针对癌症干细胞的治疗方法可能会提高康复几率。

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本文引用的文献

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