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: 10454730
• 负责人: PAUL LIMBURG
• 金额: $ 4.12万
• 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 2022-02-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454730
• 关键词: Africa; American Cancer Society; Antioxidants; Arachidonic Acids; Asia; Asians; 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/antagonist; 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) 是全球第四大常见癌症，也是癌症死亡的第二大原因。1 全球约有 990,000 人被诊断出患有 GC，其中近 75% 死于这种疾病。2 GC 还导致一种癌症最高的癌症负担，由伤残调整生命年损失决定。3 尽管自 20 世纪 30 年代以来 GC 的发病率总体下降，但预计全球每年的癌症负担到 2030 年，发病率将增加一倍，达到 2220 万例和 1310 万人死亡，其中三分之二以上的负担发生在资源有限的国家。4, 5 在美国，美国癌症协会估计 2015 年将有 24,590 例新发胃癌病例诊断后，大约 10,720 人将死于这种类型的癌症。6 一个人一生中患 GC 的平均风险约为 1 分之一。 111，男性的风险比女性高 2 至 3 倍。然而，不同国家的胃癌发病率差异很大，欠发达国家的发病率更高。2 胃癌在东亚、南欧和东欧更为常见。南美洲和中美洲的发病率最低，而非洲和北美的发病率最低。7 尽管近 60% 的新胃癌病例是在亚洲诊断的，8 据报道，与西方国家诊断的个体相比，亚洲人的结果明显更好。 9 五年 GC 存活率与日本相比，美国和欧洲低 40%。 10 由于GC死亡率与发病率之比较高，且缺乏可用于无症状个体的常规筛查方法，GC的管理仍然是一个挑战，需要进一步研究，以更全面地了解进展的生物学基础，并为个体制定化学预防策略。风险增加。 姜黄素是一种从植物姜黄根茎中提取的酚类抗氧化剂化合物，这种生物类黄酮是花生四烯酸代谢的有效抑制剂，可阻断肠粘膜中的脂氧合酶和环氧合酶活性，并发挥多种额外的免疫调节和抗氧化作用。正如最近的综述，人们认为通过多种分子机制和细胞途径具有广泛的化学预防潜力。 11 梅奥联盟的研究人员（Cruz-Correa 博士和 Morgan 博士）提议使用 Meriva（一种姜黄素脂质体封装制剂）和安慰剂对有胃癌 (GC) 风险的人群进行化学预防试验。与患有胃癌前病变的个体相比，多灶性萎缩性胃炎 (MAG) 和肠化生 (IM) 的炎症标志物（包括 DNA 损伤）会减少与安慰剂相比，服用研究药物 Meriva®（姜黄素）是一种姜黄素专利配方，其中含有膳食酚类和大豆卵磷脂（非转基因），与安慰剂相比，姜黄素含量和类姜黄素吸收量增加了 27 倍。单独姜黄素。