LIGHT DURING DARKNESS AND BREAST CANCER PROGRESSION

黑暗和乳腺癌进展期间的光

• 批准号: 6633641
• 负责人: DAVID BLASK
• 金额: $ 24万
• 依托单位: MARY IMOGENE BASSETT HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633641
• 关键词: MCF7 cell; athymic mouse; breast neoplasms; cyclic AMP; estrogen receptors; fatty acid metabolism; hormone inhibitor; hormone regulation /control mechanism; hormone therapy; laboratory rat; light adverse effect; linoleate; melatonin; neoplasm /cancer therapy; neoplastic process; nonhuman therapy evaluation; progesterone receptors; radioimmunoassay; receptor expression; visible light

DESCRIPTION (provided by applicant): The long-term goal of this research is to determine if light, present during darkness, is a risk factor for breast cancer progression. People in industrialized nations are being exposed to more artificial light during the night and the rate of breast cancer is increasing. The pineal gland hormone melatonin, which inhibits experimental human breast cancer growth, is produced during darkness; light present during darkness suppresses melatonin synthesis. The hypothesis to be tested is: Light, of the appropriate intensity, duration, timing and wavelength, present during darkness, stimulates breast cancer progression via melatonin suppression and a resultant disinhibition of tumor linoleic acid (LA) uptake and metabolism. The first aim is to measure the dose-response effects of exposure of nude female rats, bearing tissue-isolated estrogen receptor (ER)+ and progesterone receptor (PgR)+ MCF-7 human breast cancer xenografts, to different intensities of white light during darkness, on melatonin suppression in relation to tumor growth, LA metabolism and the expression of related growth signal transduction molecules (i.e., ER and PgR, melatonin receptor and cAMP). The second aim is to determine the dose-response effects of exposure of nude rats bearing MCF-7 xenografis in comparison with those bearing ER/PgR- MDA-MB-23 1 human breast cancer xenografts to different intensities of white light on melatonin suppression in relation to tumor growth. The third aim is to determine whether melatonin replacement will prevent the stimulative of effects of white light exposure during darkness on tumor growth, LA metabolism and the expression of related tumor growth signal transduction molecules. The fourth aim will test the effects of the duration and timing of light exposure during darkness on tumor growth and growth signal transduction events. This research may lead to the elucidation of "light-at-night" in conjunction with dietary fat intake as a new risk factor for breast cancer progression and to novel preventative measures for lowering breast cancer risk by combining modifications of indoor lighting and dietary fat intake with melatonin supplementation.

描述（由申请人提供）：本研究的长期目标是 确定黑暗中存在的光是否是乳腺癌的危险因素 进展。工业化国家的人们正在接触更多 夜间的人造光和乳腺癌的发病率正在增加。 松果体激素褪黑激素，可抑制实验性人类乳房 癌症的生长，是在黑暗中产生的；黑暗中存在光 抑制褪黑激素的合成。要检验的假设是：光， 适当的强度、持续时间、时间和波长，在 黑暗，通过抑制褪黑激素和促进乳腺癌进展 由此产生的肿瘤亚油酸（LA）摄取和代谢的去抑制。这 第一个目标是测量裸女暴露的剂量反应效应 大鼠，带有组织分离的雌激素受体 (ER)+ 和孕激素受体 (PgR)+ MCF-7 人乳腺癌异种移植物，不同强度的白色 黑暗中的光，褪黑激素抑制与肿瘤生长的关系，洛杉矶 代谢及相关生长信号转导分子的表达 （即 ER 和 PgR、褪黑激素受体和 cAMP）。第二个目标是确定 携带 MCF-7 异种移植物的裸鼠暴露的剂量反应效应 与携带 ER/PgR-MDA-MB-23 1 人类乳腺癌的患者进行比较 异种移植物在不同强度的白光下对褪黑激素的抑制 与肿瘤生长的关系。第三个目的是确定褪黑激素是否 更换将防止白光照射的刺激作用 黑暗期间对肿瘤生长、LA代谢及相关蛋白表达的影响 肿瘤生长信号转导分子。第四个目标将测试 黑暗期间光照的持续时间和时间对肿瘤的影响 生长和生长信号转导事件。这项研究可能会导致 阐明“夜间照明”与膳食脂肪摄入结合作为新的 乳腺癌进展的危险因素和新的预防措施 通过结合改变室内照明来降低乳腺癌风险 以及补充褪黑激素的膳食脂肪摄入量。