Tumorigenic moisturizing creams: mechanisms and active constituents

致瘤保湿霜：机制和活性成分

基本信息

批准号：
8459015
负责人：
Yaoping Lu
金额：
$ 26.27万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2015-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Sunlight-induced nonmelanoma skin cancer is the most revalent cancer in the United States with more than one million cases per year (almost as many cases as for all of the other cancers combined), and the number of these cancers has been increasing in recent years. The reasons for this increase are not known. Although most non-melanoma skin cancers are cured by surgical removal, deaths from these cancers continue to occur. We have developed a novel animal model that resembles sunlight-induced skin cancer in humans who receive heavy exposure to sunlight early in life and who develop skin cancer later in life in the absence of additional heavy sunlight exposure. In this model, SKH-1 mice are treated with low doses of UVB for 20 weeks and UVB irradiation is stopped. These mice have no tumors, but they have a high risk of developing skin tumors over the next several months in the absence of further UVB irradiation (high risk mice), and these mice can be used for evaluating tumorigenic and chemopreventive agents. In a recent study, we found that topical applications of several different commercially available moisturizing creams to UVB-pretreated high-risk mice, in the absence of further UVB irradiation, enhanced the formation of skin tumors (tumor-promoting effect). (See Lu et al in J. Invest. Dermatol. 129: 468-475, 2009.) We hypothesize that these tumorigenic commercial creams increase inflammation, stimulate proliferation, and inhibit apoptosis in the epidermis prior to tumor formation and in tumors of UVB pretreated high-risk mice. We also hypothesize that topical applications of sodium lauryl sulfate, mineral oil and petrolatum (substances present in the tumor-promoting moisturizing creams that we studied and in many other home care products) will be tumorigenic in UVB-pretreated high-risk mice. Our specific aims are: 1. Analyze the effects of topical applications of tumor-promoting moisturizing creams and their constituents on inflammation, proliferation, and apoptosis in the epidermis of SKH-1 mice pretreated with UVB for 2 weeks (short-term studies). 2. Evaluate the effects of topical applications of tumor-promoting moisturizing creams in UVB pretreated high risk mice on inflammation, proliferation, and apoptosis in the epidermis prior to tumor formation and in tumors and areas of the epidermis away from tumors in tumor-bearing mice (mechanism studies utilizing stored paraffin blocks). 3. Evaluate the tumor-promoting activity of topical applications of sodium lauryl sulfate, mineral oil and petrolatum in UVB-pretreated high-risk mice.

描述（由申请人提供）：阳光引起的非黑色素瘤皮肤癌是美国最复杂的癌症，每年超过一百万例（几乎与所有其他癌症的癌症总和一样多），近年来，这些癌症的数量一直在增加。这种增加的原因尚不清楚。尽管大多数非黑色素瘤皮肤癌通过手术切除疗法，但这些癌症的死亡仍在继续发生。我们已经开发了一种新型的动物模型，类似于人类的阳光引起的皮肤癌，他们在生命早期就受到阳光的大量暴露，并且在没有额外的阳光暴露的情况下，他们在生命后期发展了皮肤癌。在此模型中，用低剂量的UVB处理SKH-1小鼠20周，并停止UVB辐射。这些小鼠没有肿瘤，但是在没有进一步的UVB辐射（高风险小鼠）的情况下，它们在接下来的几个月内患有皮肤肿瘤的风险很高，并且这些小鼠可用于评估肿瘤性和化学预防剂。在最近的一项研究中，我们发现，在没有进一步的UVB辐射的情况下，几种不同市售的保湿霜在UVB预处理的高风险小鼠中的局部应用增强了皮肤肿瘤的形成（促进肿瘤效应）。（请参阅J.Invest。Dermatol。129：468-475，2009。）我们假设这些肿瘤性商业乳霜会增加炎症，刺激增殖并抑制肿瘤形成和UVB肿瘤肿瘤的高风险高危小鼠之前的表皮凋亡。我们还假设，硫酸钠硫酸钠，矿物油和石油的局部用途（我们研究的肿瘤促进保湿霜和许多其他家庭护理产品中存在的物质）在UVB预测的高风险小鼠中是肿瘤性的。我们的具体目的是：1。分析促进肿瘤保湿霜及其成分对用UVB预处理2周的SKH-1小鼠表皮中炎症，增殖和凋亡的局部应用（短期研究）（短期研究）。 2。评估在UVB中促进肿瘤保湿霜的局部用途的影响，预处理高风险小鼠对肿瘤形成之前的表皮以及在肿瘤和表皮区域的炎症，增殖和凋亡对肿瘤的肿瘤和肿瘤中的肿瘤区域（使用储存的肿瘤研究）的影响。 3。评估硫酸钠硫酸钠，矿物油和凡士林在UVB预测的高危小鼠中的局部促进活性。