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

胃癌(GC)是全球第四大常见癌症和第二大癌症死亡原因。1全世界约有99万人被诊断为胃癌，其中近75%死于这种疾病。2胃癌也是癌症负担最高的疾病之一，根据残疾调整后的寿命年损失来确定。3尽管自20世纪30年代以来，胃癌的发病率总体上有所下降，但到2030年，全球每年的癌症负担预计将翻一番，达到2220万例和1310万例死亡，其中超过三分之二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年将诊断出24,590例新的胃癌病例，约10,720人将死于这类癌症。6一个人一生中罹患胃癌的平均风险约为1/111，男性的风险是女性的2至3倍。然而，不同国家的胃癌发病率差异很大，在欠发达国家更高。2胃癌在东亚、南欧和东欧以及南美洲和中美洲更为常见，而发病率最低的是非洲和北美。7虽然近60%的新胃癌病例是在亚洲确诊的，但8与西方国家相比，亚洲人的预后要好得多。9美国和欧洲的五年胃癌存活率比日本低40%。 由于GC的高死亡率/发病率，以及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，需要进一步的研究，以更充分地了解进展的生物学基础，并为高危个体制定化学预防策略。 姜黄素是从植物姜黄根茎中提取的一种酚类抗氧化剂。这种生物黄酮类化合物是花生四烯酸代谢的有效抑制剂，并阻断肠粘膜中的脂氧合酶和环氧合酶活性。姜黄素发挥多种额外的免疫调节和抗氧化作用，并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，最近综述。 来自Mayo联盟的研究人员(Cruz-Correa&Morgan博士)提议对胃癌高危人群进行一项化学预防试验，使用Meriva(一种脂质体包裹的姜黄素制剂)和安慰剂。假设是，与安慰剂相比，服用姜黄素的胃癌前病变-多灶性萎缩性胃炎(MAG)和肠化生(IM)患者在服用6个月后，包括DNA损伤在内的炎症标志物将有所减少。Meriva®(姜黄素)是姜黄素的专利配方，其中包括饮食中含有大豆卵磷脂的酚类(非转基因)。姜黄素的含量和类姜黄素的吸收比单独使用姜黄素高27倍。

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.