Prevention of Oral Cancer by Strawberries with Selenium Assimilated in the Fruit

草莓中吸收的硒可预防口腔癌

基本信息

批准号：
7264122
负责人：
CHRISTOPHER M WEGHORST
金额：
$ 7.5万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/7264122
关键词：
Accounting Address Affect Animal Model Animals Anthracenes Antioxidants Apoptosis Area Berry Biological Markers California Cancer Model Carcinogens Cells Cessation of life Cheek structure Chemoprevention Chemopreventive Agent Clinical Trials Compatible Condition Consumption Contralateral Control Animal Development Diet Dietary Intervention Dimethyl Sulfoxide Dose Dysplasia Effectiveness Evaluation Event Frozen Sections Fruit Funding Hamsters Human Hyperplasia Incidence Intervention Investigation Lead Lesion Malignant Neoplasms Methods Methylcellulose Modeling Molecular Molecular Target Mouth Neoplasms Mutation Numbers Oral Oral cavity Outcome Oxidative Stress Patients Phase Population Powder dose form Premalignant Prevention Process Protocols documentation Raspberries Rate Research Resected Reverse Transcriptase Polymerase Chain Reaction Risk Saliva Selenium Smokeless Tobacco Smoker Solutions Solvents Strawberries Surface System Testing Tissues Tobacco Translating Tumor Burden United States Week angiogenesis anthracene base cancer prevention chemical carcinogen dimethylbenzanthracene feeding malignant mouth neoplasm mortality oral cancer prevention oral lesion prevent protective effect research study tumor

项目摘要

DESCRIPTION (provided by applicant): Cancers of the oral cavity account for 2.5% of cancers in the United States and are the sixth most common cancer worldwide with a five year survival of approximately 50%; the number of deaths per year has not significantly changed in the past 3 decades. Because of this high mortality rate and since present treatments are relatively ineffective, intervention methods for oral cancer must be developed and tested in animal models. An animal model of oral cancer, the hamster cheek pouch (HCP), has shown that cell and tissue changes that are involved in the cancer process are similar between humans and hamsters. Because of these similarities, we have used the hamster oral cancer model to demonstrate chemopreventive activity of black raspberries and have translated this research into Phase Ib-IIa human clinical trials. The current application expands an ongoing project funded by the California Strawberry Commission in which lyophilized strawberries (LS) are being used to inhibit formation and development of oral cancers. In the current proposal, we will evaluate the combined effect of LS and selenium on the chemoprevention of oral cancer using strawberries that have selenium incorporated during formation of the fruit. Three different protocols will be used. In the first, hamsters will be given a diet of AIN-76A pellets containing 0% or 10% powdered LS or LS-selenium (LS-Se) beginning one week prior to treatment of the HCP with a chemical carcinogen (3X/wk for 8 wks); LS and LS-Se feeding is continued through 13 wks (Complete Chemoprevention Protocol). In the second and third, HCP will be initiated with chemical carcinogen (3X/wk for 6-7 wks) and beginning 48 hrs after the last dose of carcinogen, hamsters are given a diet of AIN-76A pellets containing 0% or 10% LS or LS-Se or treated topically 3x/week with 0% or 10% LS or LS-Se (Post-initiation Protocols). Control animals receive only AIN- 76A pellets or solvent vehicle. The Post-initiation experiments will mimic a condition similar to that seen in former tobacco users. We anticipate that the strawberry powder will inhibit tumor formation when given in the diet before, during, or after carcinogen treatment, as we have observed with black raspberries. Further, based on studies showing chemopreventive activity of selenium alone, we posit that treatment with LS-Se will result in a significant enhancement of chemopreventive activity and will inhibit progression of dysplastic lesions into overt tumors. A successful outcome of the post-initiation experiments will lead to human clinical trials in high risk populations using LS or LS-Se in a vehicle compatible with human consumption.

描述（由申请人提供）：在美国，口腔癌占癌症的 2.5%，是全球第六大常见癌症，五年生存率约为 50%；过去三十年里，每年的死亡人数没有显着变化。由于死亡率高且目前的治疗相对无效，因此必须开发口腔癌的干预方法并在动物模型中进行测试。口腔癌动物模型仓鼠颊囊 (HCP) 表明，癌症过程中涉及的细胞和组织变化在人类和仓鼠之间是相似的。由于这些相似之处，我们使用仓鼠口腔癌模型来证明黑树莓的化学预防活性，并将这项研究转化为 Ib-IIa 期人体临床试验。目前的申请扩展了加州草莓委员会资助的一个正在进行的项目，其中冻干草莓（LS）被用来抑制口腔癌的形成和发展。在当前的提案中，我们将使用在果实形成过程中掺入硒的草莓来评估 LS 和硒对口腔癌化学预防的综合作用。将使用三种不同的协议。首先，在用化学致癌剂治疗 HCP 之前一周开始，仓鼠将接受含有 0% 或 10% 粉状 LS 或 LS-硒 (LS-Se) 的 AIN-76A 颗粒饮食（每周 3 次，每周 3 次）。 8周）； LS 和 LS-Se 喂养持续 13 周（完整化学预防方案）。在第二次和第三次中，HCP 将以化学致癌剂开始（每周 3 次，持续 6-7 周），并在最后一次服用致癌剂后 48 小时开始，给仓鼠喂食含有 0% 或 10% 的 AIN-76A 颗粒饲料LS 或 LS-Se 或每周 3 次用 0% 或 10% LS 或 LS-Se 局部治疗（启动后方案）。对照动物仅接受AIN-76A颗粒或溶剂载体。启动后实验将模拟与前烟草使用者类似的情况。正如我们在黑树莓中观察到的那样，我们预计在致癌物治疗之前、期间或之后在饮食中添加草莓粉将抑制肿瘤的形成。此外，根据显示单独硒的化学预防活性的研究，我们假设用 LS-Se 治疗将导致化学预防活性的显着增强，并将抑制发育不良病变进展为明显的肿瘤。启动后实验的成功结果将导致在与人类消费兼容的载体中使用 LS 或 LS-Se 在高风险人群中进行人体临床试验。