Inhibition in the progression of preinvasive lung cancer by pomegranate.

石榴抑制浸润前肺癌的进展。

基本信息

批准号：
8231278
负责人：
NAGHMA KHAN
金额：
$ 7.43万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2013-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8231278
关键词：
A/J Mouse A549 Ablation Accounting Adenocarcinoma Adenocarcinoma Cell Advanced Malignant Neoplasm Angiopoietin-2 Anthocyanins Appearance Benign Benzo(a)pyrene Butanones Cancer Patient Carcinogens Cell Culture Techniques Cells Characteristics Chemopreventive Agent Cigarette Clinical Colorectal Cancer Consumption Development Diet Early Diagnosis Ellagic Acid Employee Strikes Esters Excision Exposure to Fruit Future Glucose Goals Growth Hand Health Human Hydrolyzable Tannins In Vitro Incidence Individual Lesion Lung Lung Adenocarcinoma Lung Adenoma Lung Neoplasms MALDI-TOF Mass Spectrometry Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of prostate Morbidity - disease rate Nodule Non-Small-Cell Lung Carcinoma Nude Mice Operative Surgical Procedures Oral Patients Pomegranate Population Premalignant Prevention approach Preventive Punica granatum Quality of life Radiation Reporting Research Proposals Retinoic Acid Receptor Retinoids Risk Risk Factors Signal Pathway Signal Transduction Sirolimus Smoke Smoker Staging Structure of parenchyma of lung Testing Time Tissue Harvesting Tobacco Tobacco smoke Tobacco use Toxic effect Treatment Efficacy United States Vascular Endothelial Growth Factors Work adenoma airway epithelium angiogenesis base cancer cell cancer therapy carcinogenesis chemotherapeutic agent chemotherapy cyclooxygenase 2 delphinidin design drinking water improved in vivo lung Carcinoma lung tumorigenesis malignant breast neoplasm mortality neoplastic non-smoker novel novel therapeutic intervention pelargonidin pre-clinical prevent punicalagin punicalin research study sound tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): Lung cancer is the most common cancer in the world and tobacco smoking is the major risk factor, accounting for about 90% of the cases. Early detection of premalignant lesions or tumors appears to be an efficient approach for reducing the morbidity and mortality from lung cancer because the survival of early stage lung cancer patients is much better than that of patients with advanced cancers. Although tobacco smoking accounts for the majority of lung cancer, approximately 10% of patients with lung cancer in the United States are victims of exposure to second hand tobacco smoke. In addition, the individuals who have quit smoking (ex- smokers) are another group of people who are also at risk for developing lung cancer. Therefore, identifying novel mechanism based preventive approaches for tobacco smoke-induced lung cancer through the use of dietary substances is a highly desirable goal. The activation of mammalian targets of rapamycin (mTOR) signaling and cyclooxygenase (COX)-2 has long been associated with malignant transformation and has emerged as important cancer chemopreventive/chemotherapeutic targets. Retinoids are required for proper differentiation of lung and upper airway epithelium, and loss of expression of retinoic acid receptor (RAR)-¿ is characteristic of many lung cancers. Based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, pomegranate fruit extract (PFE) was found to contain anthocyanins (such as delphinidin, cyanidin and pelargonidin) and several hydrolysable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose). We have recently reported that PFE caused inhibition of prosurvival signaling pathways in human lung carcinoma A549 cells and inhibited tumor growth in athymic nude mice and A/J mice. Capitalizing on our compelling studies in cell-culture and in-vivo work, through this proposal, it is hypothesized that PFE will inhibit/delay lung tumor progression of adenomas to adenocarcinomas by suppressing mTOR signaling and expression of COX-2 as well as induction of retinoic acid receptor (RAR)-¿ in lungs of A/J mice. Studies will also be conducted to examine the effect of PFE on these targets in human non-small cell lung cancer cells. HEALTH RELEVANCE: Verification of this hypothesis could be extremely useful to establish the usefulness of PFE for the development of novel therapeutic approaches in improving the quality of life of early stage lung cancer patients and individuals who are ex- smokers.

描述（由申请人提供）：肺癌是世界上最常见的癌症，吸烟是主要危险因素，约占肺癌病例的 90%，早期发现癌前病变或肿瘤似乎是降低肺癌发病率和死亡率的有效方法。因为早期肺癌患者的生存率比晚期癌症患者的生存率要好得多。尽管吸烟占肺癌的大部分，但美国大约有10%的肺癌患者是接触二手烟的受害者。烟草烟雾。已经戒烟的人（戒烟者）是另一群也有患肺癌风险的人，因此，通过使用膳食物质来确定基于烟草烟雾诱发肺癌的新机制预防方法是一个非常重要的任务。雷帕霉素 (mTOR) 信号传导和环氧合酶 (COX)-2 的哺乳动物靶点的激活长期以来一直与恶性转化相关，并且已成为适当的癌症化学预防/化疗靶点。肺和上呼吸道上皮的分化，以及视黄酸受体（RAR）表达的丧失-¿是许多肺癌的特征。基于基质辅助激光解吸/电离飞行时间质谱 (MALDI-TOF MS) 分析，发现石榴果提取物 (PFE) 含有花青素（如飞燕草素、花青素和天竺葵素）。 ) ) 和几种可水解单宁（如安石榴甙、pedunculagin、安石榴甙、没食子酸酯和鞣花酸酯）我们最近报道了 PFE 抑制了人肺癌 A549 细胞中的促存活信号通路，并抑制了无胸腺裸鼠和 A/J 小鼠中的肿瘤生长。，通过该提案，我们发现PFE将通过抑制mTOR信号传导和COX-2的表达以及视黄酸受体的诱导来抑制/延迟肺肿瘤从腺瘤到腺癌的进展(RAR)-¿还将进行研究以检查 PFE 对人类非小细胞肺癌细胞中这些靶标的影响。健康相关性：验证这一假设对于确定 PFE 的有效性非常有用。开发新的治疗方法以改善早期肺癌患者和戒烟者的生活质量。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dietary agents for prevention and treatment of lung cancer.

用于预防和治疗肺癌的膳食制剂。

DOI：
发表时间：
2015-04-10
期刊：
影响因子：
9.7
作者：
Khan, Naghma;Mukhtar, Hasan
通讯作者：
Mukhtar, Hasan

Oral administration of naturally occurring chitosan-based nanoformulated green tea polyphenol EGCG effectively inhibits prostate cancer cell growth in a xenograft model.

在异种移植模型中，口服天然存在的基于壳聚糖的纳米制剂绿茶多酚 EGCG 可有效抑制前列腺癌细胞的生长。

DOI：
发表时间：
2014-02
期刊：
影响因子：
4.7
作者：
Khan, Naghma;Bharali, Dhruba J;Adhami, Vaqar M;Siddiqui, Imtiaz A;Cui, Huadong;Shabana, Sameh M;Mousa, Shaker A;Mukhtar, Hasan
通讯作者：
Mukhtar, Hasan