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

• 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
• 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

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）：恶性癌症是美国第二大死亡原因，结肠直肠癌是第二大致命癌症。老年人患结直肠癌的风险特别高，因为其发病率随年龄增长而增加。已知循环血小板随年龄变化，这可能影响包括癌症在内的各种退行性疾病。血小板与促进癌发生及其转移扩散有关，据报道，其循环数量在许多实体瘤（包括结肠直肠癌）中升高。血小板与循环癌细胞的聚集似乎保护癌细胞并促进其转移。最近对大量患者进行的低剂量抗血小板治疗（低剂量阿司匹林）对心血管风险的研究 已经报道阿司匹林对癌症形成、转移和死亡具有显著的保护作用。因此，阿司匹林已知的化学预防活性可能与其抗血小板作用有关。我们的假设是血小板活性的调节对于预防结直肠癌和抑制转移性生长是重要的。广泛使用阿司匹林进行化学预防的一个限制是其诱导急性胃肠道（GI）出血的副作用，如果不治疗，可能危及生命。这对于老年人尤其是个问题，因为高龄是NSAID诱导的GI溃疡/出血的风险因素。PI实验室开发的最近FDA批准的GI更安全的阿司匹林产品（阿司匹林-PC/PL 2200）可能提供一种方法，以提供显著的化学预防，降低GI副作用。我们建议调查：1）来自年轻和老年受试者的血小板与癌细胞之间的体外串扰，以及它们对抗血小板药物（包括各种阿司匹林制剂，特别是阿司匹林-PC和其他药剂）的响应性;和2）体内结肠癌[癌前启动的模型]和年轻和老年动物中对抗血小板药物敏感性的转移性生长。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，并可能提供一种及时安全的方法来减少老年人癌症的转移扩散。