Vitamin D/Calcium and Oxidative Stress and Inflammation Biomarkers

维生素 D/钙以及氧化应激和炎症生物标志物

• 批准号: 7660992
• 负责人: ROBERD Maner BOSTICK
• 金额: $ 7.75万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-20 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660992
• 关键词: 25-hydroxycholecalciferol-24-hydroxylase; 8-hydroxy-2' -deoxyguanosine; Address; Apoptosis; Basic Science; Bile Acids; Biological; Biological Assay; Biological Markers; Biopsy; Blood; Calcium; Cancer Etiology; Cell Cycle Regulation; Cessation of life; Chemoprevention; Chemopreventive Agent; Cholecalciferol; Clinical Trials; Colon; Colon Carcinoma; Colorectal; Colorectal Adenoma; Colorectal Cancer; Colorectal Neoplasms; Consumption; Cysteine; Data; Data Analyses; Development; Diet; Dietary Factors; Dietary Intervention; Disulfides; Double-Blind Method; E-Cadherin; Epithelium; F2-Isoprostanes; Funding; Future; Genes; Genus Cola; Glutathione; Goals; Growth Factor; Human; Image Analysis; Immunohistochemistry; Inflammation; Interferon Type II; Interleukin-6; Intervention Trial; Joints; Ki-67 Antigen; Laboratories; MLH1 gene; Malignant Neoplasms; Measurement; Measures; Methods; Mucous Membrane; Nutritional; Observational Study; Oxidative Stress; PTGS2 gene; Parents; Pathway interactions; Patients; Persons; Pilot Projects; Placebo Control; Placebos; Plasma; Prevention; Preventive; Proteins; Questionnaires; Randomized; Recurrence; Reducing Agents; Research; Resected; Risk; Sampling; Serum; Supplementation; Surrogate Endpoint; Testing; Tissues; Tumor Necrosis Factor-alpha; Vitamin D; Work; autocrine; base; colon carcinogenesis; cost; disorder risk; human TGFB1 protein; inflammatory marker; neoplastic; novel; paracrine; rectal; response

DESCRIPTION (provided by applicant): Calcium supplementation reduces colorectal adenoma recurrence, and higher serum vitamin D levels are associated with reduced risk for colorectal cancer, the second leading cause of cancer deaths in the US. However, the independent and synergistic anti-neoplastic effects of calcium and vitamin D in humans are not clear. Proposed mechanisms have included protection of colonocytes against bile acids and direct effects on cell cycle regulation. Based on basic science evidence, we hypothesize that calcium and vitamin D supplementation decrease oxidative stress and inflammation in humans in the colon epithelium and blood. We will investigate this in a pilot, adjunct study to a recently completed pilot, randomized, double-blind, placebocontrolled, 2x2 factorial chemoprevention clinical trial (termed the 'parent study'; N = 88) of supplemental calcium (2 g/day) and vitamin D3 (800 IU/day), alone and in combination vs. placebo over 6 months in patients with recently resected sporadic colorectal adenomas. The aims of the proposed pilot study are to 1) investigate the separate and joint effects of calcium and vitamin D supplementation on biomarkers of oxidative stress and inflammation in normal colorectal crypts (HNE, 8-OHdG, and COX-2 by novel automated immunohistochemistry and quantitative image analysis methods) and plasma/serum (F2-isoprostanes, PrSSCys, PrSSG, protein carbonyl, IL-6, TNFa, IFN?, and TGF¿1); 2) validate oxidative stress/inflammation biomarkers for use in human nutritional trials, including whether the biomarkers in blood are sufficiently correlated with those in normal colon tissue to be used as surrogates for those in colon tissue; and 3) investigate associations of the oxidative stress/inflammation markers with our other biomarkers of risk for colorectal neoplasms in the normal-appearing rectal mucosa. The proposed scope of work is limited to laboratory and statistical analyses using biological samples and questionnaire data from a 'parent study'. This study offers a unique, cost-effective opportunity to investigate a novel diet-colon cancer hypothesis in humans, and to validate biomarkers that will open new opportunities for investigating anti-carcinogenic effects of calcium and vitamin D and other dietary factors and whether such dietary factors may reduce risk for colorectal cancer.

描述（由申请人提供）： 补充钙可减少结直肠腺瘤复发，血清维生素D水平升高与结直肠癌风险降低有关，结直肠癌是美国癌症死亡的第二大原因。然而，钙和维生素D在人体中的独立和协同抗肿瘤作用尚不清楚。提出的机制包括保护结肠细胞免受胆汁酸和直接影响细胞周期调控。基于基础科学证据，我们假设钙和维生素D补充剂可以降低人体结肠上皮和血液中的氧化应激和炎症。我们将在最近完成的一项先导性、随机、双盲、安慰剂对照、2x2因子化学预防临床试验（称为“母研究”; N = 88）的一项先导性、辅助研究中对此进行研究，该临床试验在最近切除的散发性结直肠腺瘤患者中单独和联合使用补充钙（2 g/天）和维生素D3（800 IU/天）与安慰剂相比，为期6个月。拟定初步研究的目的是：1）研究钙和维生素D补充对正常结直肠隐窝（HNE、8-OHdG和考克斯-2，采用新型自动化免疫组织化学和定量图像分析方法）和血浆/血清（F2-异前列腺素、PrSSCys、PrSSG、蛋白羰基、IL-6、TNF α、IFN？）中氧化应激和炎症生物标志物的单独和联合作用，和TGF？1）、2）验证用于人类营养试验的氧化应激/炎症生物标志物，包括血液中的生物标志物是否与正常结肠组织中的生物标志物充分相关以用作结肠组织中的生物标志物的替代物;以及3）研究氧化应激/炎症标志物与我们的其他表现正常的直肠粘膜中的结直肠肿瘤风险生物标志物的关联。拟议的工作范围仅限于使用生物样本和“母研究”问卷数据进行实验室和统计分析。这项研究提供了一个独特的，具有成本效益的机会，以调查一种新的饮食结肠癌假说在人类中，并验证生物标志物，这将打开新的机会，调查钙和维生素D和其他饮食因素的抗癌作用，以及这些饮食因素是否可以降低结直肠癌的风险。