Inhibition of UVB-induced inflammation and carcinogenesis by black raspberry extr

黑树莓提取物抑制 UVB 诱导的炎症和致癌作用

• 批准号: 7191901
• 负责人: TATIANA M OBERYSZYN
• 金额: $ 22.5万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7191901
• 关键词: Accounting; Acute; Anthocyanins; Antioxidants; Australia; Autoimmune Process; Berry; Biological Factors; Breslow Thickness; CD4 Positive T Lymphocytes; Cellular Immunology; Cessation of life; Colon; DNA Damage; Data; Development; Dissection; Edema; Ellagic Acid; Freeze Drying; Future; General Population; Genus Cola; Graft Rejection; HIV; Heart; Immunosuppression; In Vitro; Individual; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Life; Link; Malignant Neoplasms; Malignant neoplasm of esophagus; Mission; Modeling; Mus; National Center for Complementary and Alternative Medicine; Neutrophil Infiltration; Oral; Pathology; Patients; Personal Satisfaction; Pharmaceutical Preparations; Population; Pre-Clinical Model; Preventive; Property; Raspberries; Reactive Oxygen Species; Reporting; Research Personnel; Risk; Skin; Skin Cancer; Skin Carcinoma; Skin Neoplasms; Squamous cell carcinoma; Sun Exposure; Tablets; Testing; Therapeutic immunosuppression; Topical application; Transcription Factor AP-1; Transplant Recipients; Transplantation; Tumor Cell Line; UVB induced; Ultraviolet B Radiation; Ultraviolet Rays; Vascular Endothelial Growth Factors; base; carcinogenesis; clinical application; immunosuppressed; insight; keratinocyte; novel; pill; prevent; protective effect; research study; tumor; tumor progression

DESCRIPTION (provided by applicant): Compared to the general population, transplant recipients are at greater risk for developing non-melanoma skin cancers, especially aggressive, life-threatening squamous cell carcinomas. In addition to ultraviolet light (UV) exposure, immunosuppression from multiple anti-rejection medications is implicated in the increased risk of skin cancer There is a clear need for treatments to prevent and treat skin cancer in transplant recipients. Ideally, such treatments could be administered after the damage of sun exposure has occurred, would not be administered as a pill or tablet and would have limited systemic effects. We hypothesize that topical application of black raspberry extracts (BRE) fulfill these criteria and should be explored as a treat- ment/preventive for non-melanoma skin cancer. Our preliminary data indicate that topical BRE applied after UVB exposure reduce DVB-induced inflammation and inhibit tumor development. This proposal will seek to determine the mechanisms by which inflammation is reduced. This proposal uses a murine model to test the novel hypothesis that BRE inhibit UV-induced skin inflammation and inhibit tumor formation through anti- oxidant properties, resulting in reduced keratinocyte activation, proliferation and DNA damage, reduced neutrophil infiltration and activity, and increased CD4+ T cell infiltration (Specific Aim 1). Further, we hypothesize that BRE will slow tumor progression to aggressive SCC when administered after tumors have formed (Specific Aim 2). Our team of investigators is uniquely able to test the hypothesis and perform these experiments due to complementary expertise in transplant and cellular immunology (VanBuskirk), photo- carcinogenesis and pathology (Kusewitt), skin inflammation and carcinogenesis (Oberyszyn), and the use of black raspberry extracts to prevent and treat cancer (Stoner and Hecht). The data obtained from our studies in this pre-clinical model will provide insights into the mechanisms by which BRE inhibit inflammation and tumor formation and will provide preliminary data for a more complete mechanism dissection and utilization in an R01 application. These studies are directly relevant to the RFA and the mission of NCCAM in that they begin dissection of the mechanisms by which topical application of a natural product, BRE, reduce inflammation after sun exposure and thereby inhibit skin tumor formation. These studies will also determine if BRE slow tumor progression, which will be important for future clinical applications

描述（由申请人提供）：与普通人群相比，移植受者患非黑色甲烷瘤皮肤癌的风险更大，尤其是侵略性，危及生命的鳞状细胞癌。除了暴露于紫外线（UV）外，多种抗排斥药物的免疫抑制与皮肤癌风险增加有关，显然需要治疗以预防和治疗移植受者中的皮肤癌。理想情况下，可以在发生太阳暴露的损害后可以给予此类处理，不会作为药丸或片剂给药，并且会产生有限的全身效果。我们假设黑色覆盆子提取物（BRE）的局部应用符合这些标准，应作为对非黑色素瘤皮肤癌的治疗/预防措施进行探讨。我们的初步数据表明，UVB暴露后应用的局部BRE减少了DVB诱导的炎症并抑制肿瘤的发展。该提案将寻求确定减少炎症的机制。该提议使用鼠模型来测试新的假设，即BRE抑制紫外线诱导的皮肤炎症并通过抗氧化剂特性抑制肿瘤形成，从而导致角质形成细胞的激活，增殖和DNA损伤，中性粒细胞浸润和活性减少，以及CD4+ T细胞浸没的降低（特定的CD4+ T细胞浸润）（特定于CD4+ Temple）。此外，我们假设BRE在形成肿瘤后施用后会减慢肿瘤向侵袭性SCC的进展（特定的AIM 2）。由于移植和细胞免疫学（VANBUSKIRK），光致癌和病理学（Kusewitt），皮肤炎症和癌变（oberyszyn）以及黑覆面包提取物的使用，我们的研究人员团队独特地能够检验假设并进行这些实验，并进行这些实验。从我们的研究中获得的数据获得的数据将提供有关BRE抑制炎症和肿瘤形成的机制的见解，并将为R01应用中的更完整的机制解剖和利用提供初步数据。这些研究与RFA和NCCAM的任务直接相关，因为它们开始解剖天然产物局部应用BRE，减少暴露后的炎症并抑制皮肤肿瘤的形成。这些研究还将确定BRE缓慢的肿瘤进展，这对于将来的临床应用很重要