Perinatal Breast Cancer Programming--Fat and estrogens
围产期乳腺癌规划——脂肪和雌激素
基本信息
- 批准号:6938771
- 负责人:
- 金额:$ 13.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-07-01 至 2008-05-31
- 项目状态:已结题
- 来源:
- 关键词:animal genetic material tagbioinformaticsbreast neoplasmscancer riskdevelopmental disease /disorderdietary lipidearly experienceembryo /fetusestrogensgas chromatography mass spectrometrygene expression profilinggenetically modified animalshormone regulation /control mechanismlaboratory mouselaser capture microdissectionlongitudinal animal studymammary epitheliummicroarray technologymolecular oncologymother /embryo /fetus nutritionnutrition related tagphytoestrogensplacental transferpolymerase chain reactiontumor promoters
项目摘要
DESCRIPTION (provided by applicant): The long-term goal of this research is to investigate the fetal origins of breast cancer and the role of environmental factors during early development, conception-weaning. 2 sources of estrogenic exposure relevant to man will be studied: a phytoestrogen preparation from soy mainly containing genistein and daidzein, and the ubiquitous environmental xenoestrogen 4-nonylphenol. Our hypothesis states the maternal estrogenic environment has a strong influence on risk to mammary tumorigenesis in adult life. 2 corollaries are: (a) phytoestrogens (90 ppm genistein/daidzein), in conjunction with an isocaloric 20% fat-diet having high n-3/n-6 polyunsaturated fatty acid balance, will significantly lower the risk of mammary tumors; and (b) xenoestrogen exposure (25 ppm 4-nonylphenol), in conjunction with a low dietary n-3/n-6 fatty acid balance, will promote the risk. The hypothesis will be tested in a unique mouse model for breast cancer having mammary-specific expression of a conditional mutation in the tumor suppressor Trp53 allele (flox'd p53.R270H/WAP-Cre model). The "humanized" mutant allele is permanently activated in the mammary gland epithelium exclusively in females traversing their first pregnancy-lactation cycle. This expression predisposes females to mammary tumors (-70% incidence) between ages 25-52 weeks. The project has 2 concurrent Specific Aims. (1) To investigate the effects of gestational-neonatal exposure to phyto/xenoestrogens on mammary gland development and tumorigenesis in female offspring heterozygous for the conditional p53.R270H allele reared on diets of low and high n-3/n-6 fatty acid composition. (2) Using the powerful combination of gene expression profiling with laser capture microdissection enumerate the molecular abundance profiles of epithelial end-buds and subtending ducts as foci for pre-malignant changes in the naive (virgin) and initiated (parous) mammary gland of p53.R270H/WAP-Cre females. These studies will provide new biomarker leads based in genetic regulatory networks that correlate (or anti-correlate) with altered fetal programming and pre-malignancy together with the realization of how such networks might relate functionally to the prenatal environmental risk factors in breast cancer.
描述(由申请人提供):本研究的长期目标是研究乳腺癌的胎儿起源以及环境因素在早期发育,受孕-断奶中的作用。将研究与人类相关的两种雌激素暴露来源:一种主要含有染料木素和大豆苷元的大豆植物雌激素制剂,以及普遍存在的环境外源雌激素4-壬基酚。我们的假设表明,母亲的雌激素环境对成年后乳腺肿瘤发生的风险有很大的影响。2推论是:(a)植物雌激素(90 PPM染料木素/大豆黄酮),与具有高n-3/n-6多不饱和脂肪酸平衡的20%等热量脂肪饮食相结合,将显著降低乳腺肿瘤的风险;(b)暴露于异雌激素(25 PPM的4-壬基酚),再加上饮食中n-3/n-6脂肪酸平衡过低,会增加患病风险。这一假设将在一种独特的乳腺癌小鼠模型中得到验证,该模型具有肿瘤抑制基因Trp53 (flox'd p53)等位基因条件突变的乳腺特异性表达。R270H / WAP-Cre模型)。“人源化”突变等位基因在乳腺上皮中永久激活,仅在经历第一次怀孕-哺乳周期的女性中激活。这种表达使25-52周龄的女性更易患乳腺肿瘤(发病率-70%)。该项目有两个并行的特定目标。(1)探讨妊娠期和新生儿暴露于植物/异种雌激素对条件p53杂合雌性后代乳腺发育和肿瘤发生的影响。在低和高n-3/n-6脂肪酸组成饲粮中饲养R270H等位基因。(2)利用基因表达谱与激光捕获显微解剖的强大结合,列举上皮终芽和相关导管的分子丰度谱,作为p53在幼稚(处女)和起始(分娩)乳腺中癌前病变的病灶。R270H / WAP-Cre女性。这些研究将提供基于基因调控网络的新的生物标志物线索,这些网络与改变的胎儿编程和恶性肿瘤相关(或反相关),并实现这些网络如何在功能上与乳腺癌产前环境风险因素相关。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Thomas B Knudsen其他文献
Evaluation of biologically based dose-response modeling for developmental toxicity: a workshop report.
基于生物学的发育毒性剂量反应模型的评估:研讨会报告。
- DOI:
- 发表时间:
2000 - 期刊:
- 影响因子:0
- 作者:
Christopher Lau;Melvin E. Andersen;D. Crawford‐Brown;R. Kavlock;Carole A. Kimmel;Thomas B Knudsen;Ken Muneoka;John M. Rogers;R. Setzer;Gary Smith;Rochelle W. Tyl - 通讯作者:
Rochelle W. Tyl
Thomas B Knudsen的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Thomas B Knudsen', 18)}}的其他基金
Speaker Travel & Session Cost for / Teratology Social Annual Meeting - 300.1
扬声器旅行
- 批准号:
7334533 - 财政年份:2007
- 资助金额:
$ 13.93万 - 项目类别:
Perinatal Breast Cancer Programming: fat and estrogens
围产期乳腺癌规划:脂肪和雌激素
- 批准号:
7082042 - 财政年份:2005
- 资助金额:
$ 13.93万 - 项目类别:
2004 TERATOLOGY SOCIETY MEETINGS: TRAVEL FOR STUDENTS
2004 年畸形学学会会议:学生旅行
- 批准号:
6805341 - 财政年份:2004
- 资助金额:
$ 13.93万 - 项目类别:
2003 TERATOLOGY SOCIETY MEETINGS: TRAVEL FOR STUDENTS
2003 年畸形学学会会议:学生旅行
- 批准号:
6669040 - 财政年份:2003
- 资助金额:
$ 13.93万 - 项目类别:
Response Signatures of Alcohol-Related Birth Defects
酒精相关出生缺陷的反应特征
- 批准号:
6533662 - 财政年份:2001
- 资助金额:
$ 13.93万 - 项目类别:
Response Signatures of Alcohol-Related Birth Defects
酒精相关出生缺陷的反应特征
- 批准号:
6649349 - 财政年份:2001
- 资助金额:
$ 13.93万 - 项目类别:
Response Signatures of Alcohol Related Birth Defects
酒精相关出生缺陷的反应特征
- 批准号:
6337388 - 财政年份:2001
- 资助金额:
$ 13.93万 - 项目类别:
Response Signatures of Alcohol-Related Birth Defects
酒精相关出生缺陷的反应特征
- 批准号:
6895693 - 财政年份:2001
- 资助金额:
$ 13.93万 - 项目类别:
Environmental Impact on the Embryonic mtDNA Genome
环境对胚胎 mtDNA 基因组的影响
- 批准号:
6518123 - 财政年份:1998
- 资助金额:
$ 13.93万 - 项目类别:
Environmental Impact on the Embryonic mtDNA Genome
环境对胚胎 mtDNA 基因组的影响
- 批准号:
6751933 - 财政年份:1998
- 资助金额:
$ 13.93万 - 项目类别:
相似国自然基金
膀胱癌高表达基因UPK3A的筛选、鉴定和相关研究
- 批准号:81101922
- 批准年份:2011
- 资助金额:23.0 万元
- 项目类别:青年科学基金项目
对虾白斑综合症病毒(WSSV)感染相关基因及其细胞受体的筛选和鉴定
- 批准号:30700618
- 批准年份:2007
- 资助金额:17.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Conference: Global Bioinformatics Education Summit 2024 — Energizing Communities to Power the Bioeconomy Workforce
会议:2024 年全球生物信息学教育峰会 — 激励社区为生物经济劳动力提供动力
- 批准号:
2421267 - 财政年份:2024
- 资助金额:
$ 13.93万 - 项目类别:
Standard Grant
Causes and Downstream Effects of 14-3-3 Phosphorylation in Synucleinopathies
突触核蛋白病中 14-3-3 磷酸化的原因和下游影响
- 批准号:
10606132 - 财政年份:2024
- 资助金额:
$ 13.93万 - 项目类别:
Conference: The 9th Workshop on Biostatistics and Bioinformatics
会议:第九届生物统计与生物信息学研讨会
- 批准号:
2409876 - 财政年份:2024
- 资助金额:
$ 13.93万 - 项目类别:
Standard Grant
Open Access Block Award 2024 - EMBL - European Bioinformatics Institute
2024 年开放获取区块奖 - EMBL - 欧洲生物信息学研究所
- 批准号:
EP/Z532678/1 - 财政年份:2024
- 资助金额:
$ 13.93万 - 项目类别:
Research Grant
PAML 5: A friendly and powerful bioinformatics resource for phylogenomics
PAML 5:用于系统基因组学的友好且强大的生物信息学资源
- 批准号:
BB/X018571/1 - 财政年份:2024
- 资助金额:
$ 13.93万 - 项目类别:
Research Grant
PDB Management by The Research Collaboratory for Structural Bioinformatics
结构生物信息学研究合作实验室的 PDB 管理
- 批准号:
2321666 - 财政年份:2024
- 资助金额:
$ 13.93万 - 项目类别:
Cooperative Agreement
Planning Proposal: CREST Center in Bioinformatics
规划方案:CREST生物信息学中心
- 批准号:
2334642 - 财政年份:2023
- 资助金额:
$ 13.93万 - 项目类别:
Standard Grant
Collaborative Research: IIBR: Innovation: Bioinformatics: Linking Chemical and Biological Space: Deep Learning and Experimentation for Property-Controlled Molecule Generation
合作研究:IIBR:创新:生物信息学:连接化学和生物空间:属性控制分子生成的深度学习和实验
- 批准号:
2318829 - 财政年份:2023
- 资助金额:
$ 13.93万 - 项目类别:
Continuing Grant
Circadian rhythm control of chronic pain and neuroinflammation: a bedside-to-bench study
慢性疼痛和神经炎症的昼夜节律控制:一项从床边到工作台的研究
- 批准号:
479624 - 财政年份:2023
- 资助金额:
$ 13.93万 - 项目类别:
Operating Grants
Tailoring an Optimal Immune System for Each Patient: A Café Scientifique series hosted by the Canadian Donation and Transplantation Research Program.
为每位患者量身定制最佳免疫系统:由加拿大捐赠和移植研究计划主办的 Café Scientifique 系列。
- 批准号:
485669 - 财政年份:2023
- 资助金额:
$ 13.93万 - 项目类别:
Miscellaneous Programs