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。这是非常昂贵的监测和治疗这种形式的膀胱癌。尿道对致癌物诱发的癌症高度敏感，例如来自香烟烟雾的致癌物。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，辣椒素抑制膀胱癌细胞在培养中的生长。我们已经提出，辣椒素可以是一个有效的主要化学预防剂凭借其调节致癌物质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处于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。完成拟议的实验将提供有关辣椒素作为膀胱癌的化学预防剂的潜力的证据。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以及肌肉浸润性膀胱癌的药物。长期目标是将辣椒素转化为临床药物，以降低膀胱癌相关的发病率和经济负担。移行细胞癌（TCC）是迄今为止美国最常见的膀胱癌。它是监测和治疗成本最高的癌症之一，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称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预防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.