skin(可用翻译工具辅助理解哦,也许会方便和有效率点).doc

SKINLike other tissues undergoing rapid renewal, such as the hematopoieticsystem and the intestinal epithelia, mammalianskin is highly susceptible to ionizing radiation 22. Despitethe advanced radiotherapy facilities available, high doses ofradiation (2 Gy and above) still induce early and late skineffects 2326, and unacceptable normal tissue reactionsremain the limiting factor for delivering a curative dose inradiation therapy. In humans, the epidermis is completelyrenewed approximately every 3 weeks. This high skin turnoveris maintained by different resident pools of skin stemcells that have the capacity to self-renew and also generateone or more cell lineages of the tissue (e.g., epidermis, hairfollicles, and sebaceous glands 2729. A specialized regionof the hair follicle, known as the bulge, is a major repositoryof clusters of stem cells; whereas, in the interfollicular epidermis,stem cells reside as single cells that, interspersed withmore differentiated transit amplifying (TA) cells, undergo eithersymmetric or both symmetric and asymmetric divisionsdepending on developmental stage 2934. Recently, lineagetracing experiments in adult mouse tail epidermis have suggestedthat epidermal stem cells may reside as only one typeof progenitors giving rise directly to a committed progeny,without a TA phase, at rates that ensure epidermal homeostasis35, although this remains controversial. Although theepidermis grows continuously, hair follicles are characterizedby cyclic growth that alternates periods of growth (anagen),regression (catagen), and rest (telogen) throughout life 36.In response to injury involving interfollicular epidermal stemcells, hair follicle stem cells in the bulge are recruited toparticipate in epidermal repair 37.Results from experiments involving removal, by abrasion,of actively cycling TA cells and quiescent cellsincludingstem cellsfrom the interfollicular epidermis before carcinogenictreatment suggested that the target cells for skin cancerinitiation reside in the hair follicles and, to a lesser degree, inthe interfollicular epidermis 38. In work with radiation, thesynchronous follicle growth typical of the young mouse wasexploited to demonstrate that mice exposed to radiation duringactive hair growth (anagen) had the highest susceptibilityto basal cell carcinoma (BCC), a very common human tumor,relative to mice exposed during rest phase (telogen). Becauseradiation exerts its greatest impact on rapidly proliferatingcells, this high BCC yield was attributed to the transient proliferationof follicular stem cells during irradiation 39.Nevertheless, development of different subtypes of BCC-liketumors depending on the stage of follicle growth in this studysuggested a critical role for the interfollicular epidermis, inaddition to the hair follicle bulge stem cells, in the formationof radiation-induced BCC-like tumors. Both anatomical/histologicaland immunohistochemical relationships helped toclarify the cell lineage selection in different tumors 39.The availability of monoclonal antibodies to skin cell surfacemarkers, in combination with flow sorting techniques,have made it possible to isolate and analyze human keratinocytestem cells from heterogeneous skin cell populations 40.The markers used were the adhesion molecule a6, a memberof the integrin family (a6 bri), and a second cell surfacecomponent whose expression is proliferation-related, theCD71 transferrin receptor, which allowed separation of bothstem and progenitor cells. Rachidi et al. 41 used this samecombination of markers to isolate human keratinocyte populationsfrom the interfollicular epidermis and characterized theirradiation response. These authors showed that the majority ofbasal cells, which are cycling cells that exhibit the phenotypeof progenitors and are responsible for the short-term renewalof human epidermis, are radiosensitive. In contrast, a smallpopulation of quiescent cells with characteristics of keratinocytestem cells was found to be radioresistant. Gene expressionprofiling showed repression of a network of genes functionallyrelated to apoptosis as well as specific induction of aset of genes related to DNA double strand break repair inirradiated stem cells, suggesting a possible correlation ofradioresistance with more efficient repair of DNA damageand/or reduced apoptotic response.Regarding stem cells in nonmelanoma skin cancer, Malanchiet al. 42 have recently described in mouse early squamouscell carcinomas (SCCs) a population of CSCs showingdependence on b-catenin as well as phenotypical and functionalsimilarity to normal bulge skin stem cells. Theseauthors also observed that nuclear b-catenin was more frequentthan would be predicted from a small population ofCSCs suggesting that, although b-catenin signaling is requiredfor tumorigenesis, it is not strictly a marker of CSCs. In furthertests of b-catenin signaling in human SCC cell lines,short hairpin RNA-mediated knockdown of b-catenin stronglydecreased tumor growth in xenografts, confirming the requirementof b-catenin signaling for growth of squamous skintumors. Unfortunately, no data are available on the sensitivity/resistance to radiation or chemotherapeutic agents of theseisolated CSC subpopulations.Surgical resection remains the elective treatment for BCC,while surgery and pathological monitoring are the primarymethods of treatment for cutaneous SCC, although aggressivetumors may require multimodal therapy with surgery and radiation43. This may explain the lack of available data characterizingthe sensitivity/resistance to radiation or chemotherapeuticagents of stem cells in nonmelanoma skin cancer.SKIN其他组织一样，经历着快速的更新，如造血系统和肠上皮细胞，哺乳动物皮肤是高度敏感的电离辐射22。尽管先进的放射治疗设备，高剂量的辐射（2戈瑞以上）仍引起早期和晚期皮肤的影响2326，和不能接受的正常组织反应保持的限制因素提供治疗剂量放射治疗。在人类中，表皮完全是重新大约每3周。皮肤如此高的营业额是由不同的居民皮肤干池有能力的细胞的自我更新，也产生一个或多个细胞谱系的组织（例如，表皮，毛发毛囊，皮脂腺27-29。一个专门的区域的毛囊，被称为凸起，是一个重要的资源库的干细胞群，而，在表皮干细胞作为单细胞，穿插驻留更多差异化的运输扩增细胞（TA），接受对称或对称和非对称分裂根据发育阶段2934。最近，血统跟踪实验在成年小鼠尾部表皮的建议表皮干细胞可能驻留只有一种类型祖细胞直接引起一个坚定的后代，没有TA阶段，在价格，以确保表皮平衡35，虽然这仍然是有争议的。虽然表皮持续增长，毛囊的特点通过循环增长的交替时期的增长（生长期），回归（退行期），整个生活和休息（休止期）36。受伤涉及滤泡表皮干在隆起的细胞，毛囊干细胞被招募到参加在表皮的修复37。实验结果去除，磨损，积极骑自行车的的TA细胞和静止期细胞，包括前致癌的表皮干细胞治疗建议，皮肤癌的靶细胞起始驻留在毛囊中，并在较小的程度，在表皮38。在工作中与辐射，同步卵泡发育典型的小老鼠利用证明暴露在辐射中的老鼠，在积极的头发生长（生长期）的敏感性最高基底细胞癌（BCC），一个很常见的人类肿瘤，相对于小鼠暴露在休息阶段（休止期）。因为辐射迅速增殖，发挥其最大的影响细胞，这是由于高的BCC收率瞬态增殖照射在卵泡干细胞39。然而，发展的不同亚型BCC-根据卵泡发育的阶段，在这项研究中肿瘤提出了关键作用的表皮中，在除了毛囊隆起的干细胞，在地层中辐射引起的基底细胞癌样肿瘤。解剖/组织学和免疫组化的关系帮助澄清在不同的肿瘤细胞系的选择39。单克隆抗体对皮肤细胞表面的可用性标记，在与流式分选技术相结合，