RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF MERIVA (R) AS A CANDIDATE CHEMOPREVENTION AGENT FOR GASTRIC CARCINOGENESIS

MERIVA (R) 作为胃癌候选化学预防药物的随机、双盲、安慰剂对照试验

• 批准号: 10559466
• 负责人: PAUL LIMBURG
• 金额: $ 7.4万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10559466
• 关键词: Africa; American Cancer Society; Antioxidants; Arachidonic Acids; Asia; Asian population; Atrophic Gastritis; Bioflavonoid; Biological; CXCL10 gene; Cancer Burden; Cancer Etiology; Central America; Cessation of life; Chemopreventive Agent; Country; Curcumin; DNA Damage; Developing Countries; Diagnosis; Disease; Eastern Europe; Encapsulated; Europe; Far East; Flow Cytometry; Formulation; Gastric mucosa; Genotype; Histology; Human; IL8 gene; Incidence; Indium-111; Individual; Interleukin-1 beta; Intestinal Metaplasia; Intestinal Mucosa; Investigation; Japan; Lecithin; Legal patent; Liposomes; Lipoxygenase; Malignant Neoplasms; Metabolism; Methods; Molecular; Multifocal Lesion; North America; Outcome; Participant; Pathway interactions; Persons; Phenols; Placebos; Plants; Populations at Risk; Prostaglandin-Endoperoxide Synthase; Randomized; Reporting; Research Personnel; Resources; Rhizome; Risk; Safety; South America; Southern Europe; Stomach; Survival Rate; TNF gene; Technology; Tumeric; Woman; absorption; cancer type; chemokine; cytokine; dietary; disability-adjusted life years; double-blind placebo controlled trial; gastric carcinogenesis; immunoregulation; inflammatory marker; inhibitor; magnetic beads; malignant stomach neoplasm; men; mortality; premalignant; primary endpoint; routine screening; secondary endpoint; soy; years of life lost

Gastric cancer (GC) is the 4th most common incident cancer and the 2nd leading cause of cancer death worldwide.1 Approximately 990,000 people are diagnosed with GC worldwide, of whom close to 75% die from this disease.2 GC also is responsible for one of the highest cancer burdens, as determined by disability-adjusted life years lost.3 Despite the overall decrease in the incidence of GC since the 1930s, the annual global burden of cancer is projected to double by 2030 to 22.2 million incident cases and 13.1 million deaths, with over two-thirds of the burden in resource-limited nations.4, 5 In the US, the American Cancer Society estimates that in 2015 24,590 new cases of GC will be diagnosed and approximately 10,720 individuals will die from this type of cancer.6 The average risk that a person will develop GC in his/her lifetime is about 1 in 111, with the risk being 2 to 3-fold higher in men than women. However, GC incidence rates vary dramatically across different countries and are higher in less developed countries.2 GC is more common in East Asia, Southern and Eastern Europe, and South and Central America whereas the lowest incidence rates are observed in Africa and North America.7 Although nearly 60% of the new GC cases are diagnosed in Asia,8 significantly better outcomes have been reported among Asian individuals compared to those diagnosed in Western countries.9 Five-year GC survival rates are 40% lower in the US and Europe compared to Japan.10 With the high GC mortality-to-incidence ratio and the lack of routine screening methods available for asymptomatic individuals, the management of GC remains a challenge and warrants further investigations to more fully understand the biologic basis of progression and to develop chemopreventive strategies for individuals at increased risk. Curcumin is a phenolic antioxidant compound derived from the rhizome of the plant Curcuma longa. This bioflavonoid is a potent inhibitor of arachidonic acid metabolism, and blocks both lipoxygenase and cyclooxygenase activity in the intestinal mucosa. Curcumin exerts a variety of additional immunomodulatory and antioxidant effects and is thought to have broad chemopreventive potential through a variety of molecular mechanisms and cellular pathways, as recently reviewed.11 The investigators (Drs. Cruz-Correa & Morgan) from the Mayo Consortium are proposing a chemopreventive trial on a population at risk for gastric cancer (GC) using Meriva (a liposome-encapsulated formulation of curcumin) and placebo. The hypothesis is that curcumin given to individuals with gastric precancerous lesions – multifocal atrophic gastritis (MAG) & intestinal metaplasia (IM) will have a decrease in markers of inflammation including DNA damage, as compared to placebo, after six months of taking the study agent. Meriva® (Curcumin) is a patented formula of curcumin that includes a dietary phenolic with soy lecithin (non-GMO). The curcumin content and the curcuminoid absorption is 27 fold higher when compared to curcumin alone.

胃癌（GC）是全球范围内癌症死亡的第四个最常见的癌症。1大约有990,000人被诊断为全球GC，其中近75％死于这种疾病。2GC还造成了最高的癌症燃烧症之一，尽管癌症丧失了最高的癌症，但由于全球疾病的整体损失了3次，但在整体上燃烧了一年一度的癌症。到2030年至222万事件案件和1310万人死亡，其中三分之二以上的燃烧在资源有限的国家中燃烧。4，5在美国，美国癌症学会估计，2015年24,590例新的GC案件将被诊断出来，而大约10,720个人将因这种癌症而死亡的平均风险较高。男人比女人。然而，在不同国家的GC事件率差异很大，在较不发达国家。2GC在东亚，南部和东欧以及南美以及中美洲更为普遍，而在非洲和北美地区观察到最低的发病率在非洲和北美地区都有最低的发病率。尽管在亚洲，几乎60％的新GC案件在亚洲诊断出了五个五年中的五个国家，但据报道，五年级的人均在ASIAN中诊断出的率很高。与日本相比，美国和欧洲10 由于GC死亡率高的生命率和缺乏适用于非对称个体的常规筛查方法，GC的管理仍然是一个挑战，并需要进一步研究，以更充分地了解进展的生物学基础，并为增加风险增加的个体制定化学预防策略。 姜黄素是一种酚类抗氧化剂化合物，源自植物姜黄的根茎。该生物黄酮是蛛网膜酸代谢的潜在抑制剂，并阻止肠粘膜中的脂氧合酶和环氧酶活性。姜黄素具有各种其他免疫调节和抗氧化作用，被认为通过各种分子机制和细胞途径具有广泛的化学预防潜力。111111111111 梅奥联盟（Mayo Consortium）的研究人员（Cruz-Correa＆Morgan博士）使用Meriva（姜黄素囊体已囊括）和安慰剂进行了针对患有胃癌风险（GC）的人群的化学预防试验。假设是，给予胃前癌病变的个体 - 多灶性萎缩性胃炎（MAG）和肠道化生型（IM）将减少六个月的研究剂后，与安慰剂相比，包括DNA损伤（包括DNA损伤）的标记物将减少包括DNA损伤的标志。 Meriva®（姜黄素）是姜黄素的专利配方，其中包括与大豆卵磷脂（非GMO）的饮食酚类酚素。与单独的姜黄素相比，姜黄素含量和姜黄素滥用量高27倍。