CLINICAL TRIAL: DFMO/SULINDAC PHASE III

临床试验：DFMO/SULINDAC III 期

• 批准号: 7724987
• 负责人: FRANK MEYSKENSJR
• 金额: $ 0.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724987
• 关键词: Adenomatous Polyps; Adverse effects; Affect; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Clinical Chemoprevention; Clinical Trials; Colon Carcinoma; Colorectal; Colorectal Cancer; Computer Retrieval of Information on Scientific Projects Database; DL-alpha-Difluoromethylornithine; Development; Dietary Factors; Disease; Disease regression; Dose; Effectiveness; Epidemiologic Studies; Funding; Grant; Growth; Institution; Intake; Intervention; Investigation; Malignant Neoplasms; Molecular; Nature; Pathogenesis; Pathway interactions; Pharmaceutical Preparations; Phase; Polyamines; Polyps; Research; Research Personnel; Resources; Series; Signal Pathway; Source; Sulindac; Tissues; United States National Institutes of Health; adenoma; carcinogenesis; inhibitor/antagonist

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adenomatous polyps are generally regarded as precursors to colorectal cancer and relatively late surrogates in the carcinogenic pathway to the development of these malignancies. Etiologic and experimental investigations have established the critical nature of definable molecular changes precedent to and during pathogenesis of the disease that leads to abnormal signaling pathways and defective growth control. Extensive epidemiologic studies have identified numerous dietary and non-dietary factors that affect adenoma and colorectal cancer development, including regular intake of non-steriodal anti-inflammatory drugs (NSAIDs). Experimental interventions in several animal models have demonstrated that NSAIDs as well as the polyamine synthesis inhibitor, difluoromethylornithine (DFMO), inhibit carcinogenesis including adenoma formation and colon cancer. We and others have performed Phase I, IIa and IIb clinical chemoprevention trials of DFMO and in a series of studies that have established its effectiveness in lowering the polyamine content of colorectal tissue at doses of DFMO that are almost completely free of side effects. The NSAID and sulindac has been shown to cause regression of FAP and sporadic associated polyps and its side effects profile is widely understood.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 腺瘤性息肉通常被认为是结直肠癌的前兆，并且是这些恶性肿瘤发展的致癌途径中相对较晚的替代物。 病因学和实验研究已经确定了可定义的分子变化的关键性质，导致异常信号传导途径和缺陷的生长控制的疾病的发病机制之前和期间。 广泛的流行病学研究已经确定了许多影响腺瘤和结直肠癌发展的饮食和非饮食因素，包括定期摄入非甾体抗炎药（NSAID）。 在几种动物模型中的实验干预已经证明，NSAID以及多胺合成抑制剂二氟甲基鸟氨酸（DFMO）抑制致癌作用，包括腺瘤形成和结肠癌。 我们和其他人已经进行了DFMO的I期、IIa期和IIb期临床化学预防试验，并在一系列研究中确定了DFMO在几乎完全无副作用的剂量下降低结直肠组织多胺含量的有效性。 NSAID和舒林酸已被证明可导致FAP和散发性相关息肉的消退，其副作用特征已被广泛理解。