Capsaicin for chemoprevention of transition cell carcinoma of the bladder

描述(申请人提供)：膀胱移行细胞癌是一种高度复发和最常见的膀胱癌形式在美国。监测和治疗这种形式的膀胱癌非常昂贵。尿路上皮对致癌物诱发的癌症非常敏感，例如香烟烟雾中的致癌物。我们的目标是开发自然产生的化学预防药物来预防膀胱癌。我们的初步数据表明，辣椒素在培养中可以抑制膀胱癌细胞的生长。我们认为辣椒素可以通过调节致癌物质代谢和解毒酶而成为一种有效的主要化学预防药物。我们还提出，在膀胱癌的临床前模型中，辣椒素可以通过选择性地诱导氧化应激下的癌细胞凋亡来抑制肿瘤生长。拟议实验的完成将为辣椒素作为膀胱癌化学预防药物的潜力提供证据。这些数据将允许提交后续的提案，测试辣椒素作为预防复发移行膀胱癌和肌肉浸润性膀胱癌的药物。长期目标是临床翻译辣椒素，以降低与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。在这个试点方案中，我们将测试这样一个前提，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防止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.