Capsaicin for chemoprevention of transition cell carcinoma of the bladder

描述（由申请人提供）：膀胱移行细胞癌是一种高度复发的膀胱癌，是美国最常见的膀胱癌。监测和治疗这种形式的膀胱癌非常昂贵。尿路上皮对致癌物如香烟中的致癌物非常敏感。我们的目标是开发自然发生的化学预防剂来预防膀胱癌。我们的初步数据表明，辣椒素在培养中抑制膀胱癌细胞的生长。我们提出辣椒素可以作为一种有效的一级化学预防剂，因为它具有调节致癌物代谢和解毒酶的能力。我们还提出辣椒素可以通过选择性诱导氧化应激下的癌细胞凋亡来抑制膀胱癌临床前模型中的肿瘤生长。该实验的完成将为辣椒素作为膀胱癌化学预防剂的潜力提供证据。这些数据将允许提交后续提案，以测试辣椒素作为预防复发性移行性膀胱癌和肌肉浸润性膀胱癌的药物。长期目标是辣椒素的临床转化，以减少膀胱癌相关的发病率和经济负担。移行细胞癌（TCC）是目前美国最常见的膀胱癌。它是监测和治疗费用最高的癌症之一；因此是一个巨大的经济负担。在这个试点提案中，我们将测试一个前提，即在辣椒中发现的一种名为辣椒素的天然化合物可以通过改变膀胱癌细胞的细胞生存环境来阻止TCC的发展。

DESCRIPTION (provided by applicant): Transitional cell carcinoma of the bladder is a highly recurrent and the most common form of bladder cancer in the United States. It is very expensive to monitor and treat this form of bladder cancer. The urothelium is highly susceptible to carcinogen-induced cancer such as carcinogens from cigarette smoke. Our goal is to develop naturally occurring chemopreventive agents to prevent bladder cancer. Our preliminary data suggest that capsaicin inhibits the growth of bladder cancer cells in culture. We have proposed that capsaicin can be an effective primary chemoprevention agent by virtue of its ability to modulate carcinogen metabolism and detoxification enzymes. We have also proposed that capsaicin can inhibit tumor growth in a preclinical model of bladder cancer by selectively inducing apoptosis in cancer cells that are under oxidative stress. Completion of the proposed experiments will provide evidence regarding the potential of capsaicin as a chemopreventive agent for bladder cancer. This data will allow submission of subsequent proposals to test capsaicin as an agent to prevent recurrent transitional bladder cancer as well muscle invasive bladder cancer. The long term goal is clinical translation of capsaicin to decrease morbidity and economic burden related to bladder cancer. Transitional cell carcinoma (TCC) is by far the most frequently diagnosed bladder cancer in the US. It is one of the most expensive cancers to monitor and treat; and therefore a great economic burden. In this pilot proposal we will test the premise that a naturally occurring compound called capsaicin found in chili peppers can prevent TCC development by changing the cell survival milieu of bladder cancer cells.