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，烟草吸烟是主要危险因素，约占病例的90％。早期发现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存活比晚期癌症患者的生存率要好得多。尽管烟草吸烟占大部分肺癌，但美国大约10％的肺癌患者在暴露于二手烟草烟雾中令人惊讶。此外，戒烟的人（吸烟者）是另一组患有肺癌风险的人。因此，通过使用饮食物质来确定基于机制的新型预防方法是烟草烟雾诱导的肺癌。雷帕霉素（MTOR）信号传导和环氧酶（COX）-2的哺乳动物靶标长期以来一直与恶性转化有关，并且已经成为重要的癌症化学预防/化学治疗靶标。类维生素类似于肺和上呼吸道上皮的适当分化所必需的，视网膜上的肺酸受体（RAR）的表达丧失是许多肺癌的特征。 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 pelagonidin) and several hydrolysable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of葡萄糖）。我们最近报道说，PFE在人类肺癌A549细胞中引起了抑制PROVIVAL信号通路，并抑制了胸骨裸鼠和A/J小鼠的肿瘤生长。通过这项提案来利用我们在细胞培养和体内工作中的引人注目的研究，可以假设PFE将通过抑制Cox-2的MTOR信号传导和表达Cox-2的MTOR信号传导和视黄酸受体（RAR）的诱导（RAR） - 在A/J MICE的肺中抑制腺癌的肺肿瘤进展。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：对这一假设的验证对于建立PFE在开发新型治疗方法方面的有用性对于改善早期肺癌患者和前吸烟者的个人的生活质量而言非常有用。