苹果手机的邮箱怎么用:JCI：炎症和癌症敏感性之间的联系 - 生物研究-生物谷

十多年来，美国宾夕法尼亚州大学医学院的Wafik  S.El-Deiry教授一直都在研究一种癌症靶向分子TRAIL和它的分子搭档。TRAIL通常是由免疫细胞产生，能够通过与种类表面一种特化的受体结合来抑制种类的扩散。 

在免疫力常常被抑制的癌症患者中，不能产生足够量的TRAIL，因此种类不能被抑制。 

就在最近，El-Deiry和同事首次证实TRAIL受体和癌症敏感性之间的联系。这项研究的结果发表在12月13日的《临床检查杂志》（ Journal  of  Clinical  Investigation ）网络版，2008年1月发表在印刷版上。出乎意料的是，他们还发现了炎症和癌症敏感性之间的一种由Trail介导的联系。   

与对照小鼠相比，细胞上缺失TRAIL受体的小鼠，在进行化疗或放疗后，其肝脏和其他器官中形成更多、更大的肿瘤。研究组还繁育了TRAIL敲除小鼠。与对照相比，它们的后代发生了更多的肝脏肿瘤。这是证实肿瘤死亡诱导TRAIL受体的丧失导致癌症敏感性的首个直接的活体证据。   

当完好无缺时，TRAIL和它的受体能够减少炎症细胞和导致癌症的分子。新的癌症模型暗示出炎症与癌症直接的一种联系。   

现在，El-Deiry和他的研究组增在肿瘤组织中寻找炎症分子，从而希望能够了解癌症和炎症如何相互协作。

生物谷推荐英文原文：

J. Clin. Invest. 117:3658-3660 (2007). doi:10.1172/JCI34251.

Targeting mutant p53 shows promise for sunscreens and skin cancer

Wafik S. El-Deiry

Department of Medicine, Division of Hematology/Oncology, Departmentof Genetics, Department of Pharmacology, Abramson Comprehensive CancerCenter, and Institute for Translational Medicine and Therapeutics,University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania, USA.

Address correspondence to: Wafik S. El-Deiry, Department ofMedicine, University of Pennsylvania School of Medicine, 415 CurieBlvd., CRB 437, Philadelphia, Pennsylvania 19104, USA. Phone: (215)898-9015; Fax: (215) 573-9139; E-mail: wafik@mail.med.upenn.edu.

Chronic exposure to UV light is a risk factor for skin cancer inwhich signature mutations in the p53 tumor suppressor gene occur due toDNA damage and contribute to cancer development. In this issue of theJCI, Tang et al. report on their study of a nonimmunodeficient mousemodel of UVB-induced skin cancer and human skin carcinoma cells and showthat the mutant p53 conformation–modifying drug CP-31398 not onlytreats these tumors but also prevents them (see the related articlebeginning on page 3753). These studies have important implications forchemoprevention as well as therapy of common, mutant p53–driven tumors.

According to the American Cancer Society (1), most of the more than 1million cases of nonmelanoma skin cancer diagnosed yearly in the UnitedStates are considered to be sun related. Nonmelanoma skin cancer, whichis the most common type of cancer affecting humans, occurs in eitherbasal cells or squamous cells, and cancers typically occur insun-exposed areas. Most skin cancers are caused by UV light exposure ofthe skin to sunlight or man-made tanning lamps (1). There is strongepidemiologic evidence supporting a relationship between UV lightexposure and nonmelanoma skin cancer and growing evidence of arelationship between indoor tanning and melanoma (2).

Figure 1
Targeting mutant p53 to prevent ortreat UV light–induced skin cancer. UV light exposure from brightsunlight or tanning beds leads to p53 mutations that contributeto skin cancer development in most of the 1 million individualsdiagnosed with nonmelanoma skin cancer in the US each year. In a reportin this issue of the JCI, Tang et al. (17) demonstrate thatCP-31398 (13) can prevent UVB-induced tumor development as well as serveas an effective treatment for tumors that develop in an immunocompetentmouse model. CP-31398 appears to promote apoptosis by restoringwild-type p53 activity to mutated p53, leading to increased proapoptoticBax expression, reduced antiapoptotic Bcl2 expression, and cytochrome c release from mitochondria. The inset shows the spectrum of p53mutations observed in human squamous cell cancer of the skin that isassociated with UVB exposure (UMD p53 mutation database:http://p53.free.fr/Database/p53_cancer/p53_skin.html). Mutations occurat particular hot spots with greater frequency, leading to loss of p53tumor suppressor function. BCC, basal cell carcinoma.

全文链接：

http://www.jci.org/cgi/content/full/117/12/3658?