Prevention of Bladder Cancer with Broccoli Sprouts

用西兰花芽预防膀胱癌

• 批准号: 6858819
• 负责人: YUESHENG ZHANG
• 金额: $ 23.42万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858819
• 关键词: Cruciferae; antineoplastics; apoptosis; biomarker; bladder neoplasm; cancer prevention; carcinogenesis; cell growth regulation; chemical carcinogen; chemoprevention; detoxification; enzyme activity; enzyme induction /repression; glucuronosyltransferase; glutathione transferase; human tissue; laboratory rat; nonhuman therapy evaluation; nutrition aspect of cancer; nutrition related tag; oral administration; plant extracts; sulfoxide; tissue /cell culture; urinary bladder epithelium

DESCRIPTION (provided by applicant): This project focuses on the cancer preventive activity of broccoli sprout extracts in the bladder. The hypothesis to be tested is that broccoli sprout extracts are able to suppress tumorigenesis in the bladder by inducing carcinogen-detoxifying enzymes, inducing apoptosis, and inhibiting cell proliferation, all of which contribute, perhaps synergistically, to the prevention of carcinogenesis. Molecular markers relevant to these biological events, as well as inhibition of tumorigenesis will be studied. Broccoli sprouts are the richest plant source of sulforaphane, which is known to possess the above-described chemopreventive mechanisms. Both sulforaphane and broccoli sprout extracts have been shown to inhibit tumorigenesis in animal models (non-bladder tissues). Particularly, ingested sulforaphane in humans is disposed rapidly and concentrated in urine, making bladder epithelial cells probably the most exposed cells to sulforaphane in the body. The overwhelming majority of bladder cancers originate from the epithelial cells. Aim 1 is to determine the effect of broccoli sprout extracts on the expression of critical Phase 2 detoxification enzymes in cultured human bladder epithelial cells. Glutathione transferase and UDP-glucuronosyl-transferase, whose deficiencies have been linked to bladder carcinogenesis, will be examined using both enzyme activity analysis and Western blot analysis. Aim 2 is to determine the effect of broccoli sprout extracts on apoptosis and cell cycle regulation in cultured human bladder epithelial cells. The biomarkers include nuclear DNA fragmentation, activation of selected caspases, cell cycle change and related cell cycle regulators, using both flow cytometry and Western blot analysis. Aim 3 is to determine the in vivo cancer chemopreventive activity of broccoli sprout extracts in the rat bladder. Aim 3a is designed to determine the effect of orally administered broccoli sprout extracts on Phase 2 enzymes, apoptosis, and cell proliferation in bladder epithelia. Biomarkers, including the two Phase 2 enzymes listed above, plus the TUNEL and PCNA assays, will be evaluated immunohistochemically. Aim 3b is to determine the effect of orally administered broccoli sprout extracts on N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis. Tumor incidence, tumor multiplicity, and the nature of each tumor will be determined.

描述（由申请人提供）：该项目的重点是西兰花芽提取物在膀胱中的癌症预防活性。有待检验的假设是，西兰花芽提取物能够通过诱导致癌物解毒酶、诱导细胞凋亡和抑制细胞增殖来抑制膀胱中的肿瘤发生，所有这些可能协同地有助于预防癌发生。将研究与这些生物学事件相关的分子标志物以及对肿瘤发生的抑制。西兰花芽是萝卜硫素最丰富的植物来源，已知萝卜硫素具有上述化学预防机制。萝卜硫素和西兰花芽提取物已被证明可以抑制动物模型（非膀胱组织）中的肿瘤发生。特别是，摄入的莱菔硫烷在人体中被迅速处置并浓缩在尿液中，使得膀胱上皮细胞可能是体内暴露于莱菔硫烷最多的细胞。绝大多数膀胱癌起源于上皮细胞。目的1是确定西兰花芽提取物对培养的人膀胱上皮细胞中关键的第二阶段解毒酶表达的影响。将使用酶活性分析和蛋白质印迹分析来检查谷氨酰胺转移酶和UDP-葡萄糖醛酸基转移酶，其缺陷与膀胱癌发生有关。目的2：研究西兰花芽提取物对体外培养的人膀胱上皮细胞凋亡及细胞周期的影响。生物标志物包括核DNA片段化、选定的半胱天冬酶的激活、细胞周期变化和相关的细胞周期调节剂，使用流式细胞术和Western印迹分析。目的3：研究西兰花芽提取物对大鼠膀胱癌的化学预防作用。目的3a旨在确定口服西兰花芽提取物对膀胱上皮中的2相酶、凋亡和细胞增殖的影响。将对生物标志物（包括上述两种II期酶以及TUNEL和PCNA测定）进行化学评价。目的3b是确定口服西兰花芽提取物对N-丁基-N-（4-羟丁基）亚硝胺诱导的膀胱肿瘤发生的影响。将确定肿瘤发生率、肿瘤多样性和每种肿瘤的性质。

项目成果

Atherosclerotic neovasculature MR imaging with mixed manganese-gadolinium nanocolloids in hyperlipidemic rabbits.

使用混合锰钆纳米胶体对高脂血症兔进行动脉粥样硬化新生血管 MR 成像。

• DOI: 10.1016/j.nano.2014.12.008
• 发表时间: 2015-04
• 期刊: Nanomedicine : nanotechnology, biology, and medicine
• 作者: Wang K;Pan D;Schmieder AH;Senpan A;Caruthers SD;Cui G;Allen JS;Zhang H;Shen B;Lanza GM
• 通讯作者: Lanza GM

Molecular imaging with computed tomography.

计算机断层扫描分子成像。

• DOI: 10.1002/cmmi.1581
• 发表时间: 2014
• 期刊: Contrast media & molecular imaging
• 作者: Lanza,GregoryM;Pan,Dipanjan
• 通讯作者: Pan,Dipanjan

alphaVbeta3-targeted copper nanoparticles incorporating an Sn 2 lipase-labile fumagillin prodrug for photoacoustic neovascular imaging and treatment.

• DOI: 10.7150/thno.10014
• 发表时间: 2015
• 期刊: Theranostics
• 影响因子: 12.4
• 作者: Zhang R;Pan D;Cai X;Yang X;Senpan A;Allen JS;Lanza GM;Wang LV
• 通讯作者: Wang LV

Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide.

给予三氧化二砷的小鼠口腔鳞状细胞癌 EGFR 的近红外成像

• DOI: 10.1371/journal.pone.0046255
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Zhang L;Wang K;Zhao F;Hu W;Chen J;Lanza GM;Shen B;Zhang B
• 通讯作者: Zhang B

Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers.

混合锰钆纳米胶体中表面和核心包埋金属之间的协同作用可为稀疏生物标志物提供更安全的 MR 成像。

• DOI: 10.1016/j.nano.2014.12.009
• 发表时间: 2015-04
• 期刊: Nanomedicine : nanotechnology, biology, and medicine
• 作者: Wang K;Pan D;Schmieder AH;Senpan A;Hourcade DE;Pham CT;Mitchell LM;Caruthers SD;Cui G;Wickline SA;Shen B;Lanza GM
• 通讯作者: Lanza GM