Effects of Antiplatelet Drugs on Colon Cancer in the Elderly

抗血小板药物对老年人结肠癌的影响

基本信息

批准号：
8829798
负责人：
LENARD M LICHTENBERGER
金额：
$ 16.63万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8829798
关键词：
Acute Adhesions Adverse effects Affect Age Age-Years Animals Anti Inflammatory Analgesics Antihypertensive Agents Antiplatelet Drugs Apoptosis Aspirin Azoxymethane Biological Models Bleeding time procedure Blood Platelets Cancer Cell Growth Cancer Etiology Cancer Model Cancer Patient Cause of Death Cells Cessation of life Chemoprevention Chemopreventive Agent Clinical Clinical Research Coagulants Colon Carcinoma Colorectal Colorectal Cancer Degenerative Disorder Dipyridamole Disease Distant Dose Drug Costs Drug Formulations Drug toxicity Drug usage Effectiveness Elderly Endothelium Epithelial Extravasation FDA approved Family Gastrointestinal tract structure Goals Grant Growth Growth Factor Health Healthcare Hemorrhage Human Immune In Vitro Incidence Killer Cells Knowledge Label Laboratories Lecithin Life Malignant - descriptor Malignant Neoplasms Mesenchymal Meta-Analysis Metformin Modeling Movement Mus Neoplasm Circulating Cells Neoplasm Metastasis Non-Steroidal Anti-Inflammatory Agents Oncologist PTGS2 gene Patients Pharmaceutical Preparations Platelet Activation Platelet Count measurement Platelet aggregation Platelet-Derived Growth Factor Population Process Proliferating Propranolol Recommendation Reporting Risk Risk Factors Risk Reduction Role Sales Second Primary Cancers Site Solid Neoplasm Surface Testing Thrombosis Tissues Transforming Growth Factors Ulcer Vascular Endothelial Growth Factors age effect age related aged angiogenesis cancer cell cancer diagnosis cancer initiation carcinogenesis cardiovascular risk factor cell growth chemotherapeutic agent circulating cancer cell clopidogrel colorectal cancer prevention diabetic disorder risk gastrointestinal human subject in vivo juvenile animal mortality neoplastic cell patient population population based prevent response thrombocytosis treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Malignant cancers are the second leading cause of death in the USA with colorectal cancer being the second most fatal cancer. The elderly population is particularly at risk for colorectal cancer as its incidence increases with age. Circulating platelets are known to change with age which may affect a variety of degenerative diseases including cancers. Platelets are implicated in the promotion of carcinogenesis and its metastatic spread, and their circulating numbers are reported to be elevated in a number of solid tumors including colorectal cancer. Platelet aggregation with circulating cancer cells appears to protect the cancer cells and promote their metastasis. Recent studies of large populations of patients on low dose antiplatelet therapy (low dose aspirin) for cardiovascular risk reduction, have reported that aspirin confers significant protection against cancer formation, metastases and death. Thus, it is possible that the known chemopreventive activity of aspirin may be related to its antiplatelet action. Our hypothesis is that modulation of platelet activity i important for prevention of colorectal cancer and suppression of metastatic growth. One limitation to the widespread use of aspirin for chemoprevention is its side effect to induce acute gastrointestinal (GI) bleeding that may become life threatening if untreated. This is particularly problem for the elderly, as advanced age is a risk factor for NSAID-induced GI ulceration/bleeding. A recently FDA-approved aspirin product that is GI- safer (Aspirin-PC/PL2200) developed by the PI's laboratory may offer a means to provide significant chemoprevention with reduced GI side effects. We propose to investigate: 1) the in vitro cross-talk between platelets from young and elderly subjects and cancer cells, and their responsiveness to antiplatelet drugs, including various aspirin formulations, notably Aspirin-PC, and other agents; and 2) an in vivo colon cancer [models of both pre-cancer initiation] and metastatic growth in young and old animals for sensitivity to antiplatelet drugs. These studies will contribute to knowledge about the role of platelets in chemoprevention of colorectal cancer in the elderly, and may offer a timely and safe approach to reduce the metastatic spread of cancer in the elderly.

描述（由申请人提供）：恶性癌是美国第二大死亡原因，大肠癌是第二大致命癌。随着年龄的增长，老年人群尤其面临着结直肠癌的风险。众所周知，循环血小板会随着年龄的增长而变化，这可能会影响包括癌症在内的各种退化性疾病。血小板与癌发生及其转移扩散有关，据报道，在包括大肠癌在内的许多实体瘤中，它们的循环数量升高。循环癌细胞的血小板聚集似乎可以保护癌细胞并促进其转移。对低剂量抗血小板治疗（低剂量阿司匹林）的大量患者人群的最新研究针对心血管风险减少的报道说，阿司匹林赋予了对癌症形成，转移和死亡的重大保护。因此，阿司匹林的已知化学预防活性可能与其抗血小板作用有关。我们的假设是，调节血小板活性I对于预防结直肠癌和抑制转移性生长很重要。广泛使用阿司匹林进行化学预防的局限性是诱导急性胃肠道（GI）出血的副作用，如果未经治疗，可能会威胁生命。对于老年人来说，这尤其是问题，因为高级年龄是NSAID引起的胃肠道溃疡/出血的危险因素。 PI的实验室开发的近期FDA批准的Asprin产品（Asvirin-PC/PL2200）可能会提供一种提供明显的化学预防效果，并减少GI副作用。我们建议研究：1）年轻和老年受试者和癌细胞血小板之间的体外交叉词，以及它们对抗血小板药物的反应，包括各种阿司匹林制剂，尤其是阿司匹林-PC和其他药物； 2）一种体内结肠癌[癌前起始模型]和年轻动物的转移性生长，以敏感抗血小板药物。这些研究将有助于了解血小板在老年人结直肠癌化学预防中的作用，并可能提供及时，安全的方法来减少癌症在老年人中的转移性传播。