Recording the natural history of cancer progression using a Crainbow model of HER2+ cancer
使用 HER2 癌症的 Crainbow 模型记录癌症进展的自然史
基本信息
- 批准号:10437462
- 负责人:
- 金额:$ 9.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-27 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AwardBehaviorBiological ModelsBlood VesselsBreastCellsDataDetectionDiagnosisDiseaseERBB2 geneEarly DiagnosisExtracellular MatrixFosteringFundingFutureHomeostasisImageImaging TechniquesImmuneImmune systemIndolentLesionMalignant NeoplasmsMammary NeoplasmsMammary glandMethodologyMethodsModelingMolecularMonitorMusMyoepithelial cellNatural HistoryNeoplasm MetastasisNeoplasmsNormal tissue morphologyOncogenesOperative Surgical ProceduresOutcomePhasePopulationPrimary NeoplasmProtein IsoformsResearch DesignResearch InfrastructureResearch PersonnelResolutionRoleRosaniline DyesScreening for cancerSideSomatic MutationStreamSurgical OncologistTimeTrainingbasebreast cancer progressionbreast cancer survivalcancer cellcancer invasivenesscell behaviorcell motilityclinically relevantexperimental studyimaging modalityin vivoinnovationintravital imagingintravital microscopymacrophagemalignant breast neoplasmmigrationmouse modelmultiphoton imagingnovelpremalignantpublic health relevanceserial imagingtumortumor growthtumor microenvironmenttumor progression
项目摘要
PROJECT SUMMARY/ABSTRACT
Background: The step-wise accumulation of somatic mutations and progressive changes to cell behavior
provides a rationale for the cancer screening era. However, this fails to explain de novo diagnosis of lethal
metastatic disease in the apparent absence of screen detectable precancerous lesions. Accumulating evidence
suggests that invasive cancers may initiate without a prolonged and detectable precancerous phase. In addition,
proliferative lesions do not deterministically progress, suggesting that many early cancers are overtreated.
Although a dramatic increase in early-detection has been observed, a similar dramatic decrease in lethal
metastatic disease has not been observed. Some have even argued that many screen-detected early lesions
spontaneously resolve or regress. In contrast, the most lethal cancers escape detection and metastasize prior
to detection.
Hypothesis: We hypothesize that cancer progression, like normal tissue homeostasis, is stochastic and subject
to defined spatial and microenvironmental constraints.
Specific Aims: Aim 1. To define the homeostatic principles underlying the progression of breast cancer in a
mouse model of HER2+ breast cancer. Aim 2. To dissect the role of HER2 isoforms on the metastatic cascade
of breast tumors.
Study design/Methods: Here we will use a proven cancer rainbow modeling system for visualizing and
analyzing tumor growth rates in vivo. State-of-the-art multiphoton live imaging will be used to image and quantify
tumor progression potential in space and time within the mammary gland along with microenvironmental features
(ECM, macrophages, blood vessels). Longitudinal imaging over eight weeks will capture the rates of tumor
progression and the origin of invasive breast cancers in an in vivo and immune intact mouse model.
Relevance: More than six decades ago, surgical oncologists seeking to explain why earlier surgical intervention
had not improved breast cancer survival, postulated that adaptations between the tumor and host set the
trajectory of an invasive cancer many years before diagnosis. Proponents argued that the formative early years
of tumor-TME adaptation had already destined some tumors to become invasive and lethal. In addition, many
breast cancer lesions may actually regress suggesting that cancer progression may be stochastic. Novel imaging
modalities and sophisticated tumor lineage training strategies are needed to solve this challenging problem. Our
experiments utilizing mouse models and high-resolution longitudinal imaging during the course of tumor
progression will determine whether cancer progression is deterministic or not, adding an important value towards
understanding breast cancer progression.
项目摘要/摘要
背景:体细胞突变的逐步积累和细胞行为的渐进性变化
为癌症筛查时代提供了理论基础。然而,这不能解释致命的从头诊断。
明显缺乏筛查可检测到的癌前病变的转移性疾病。积累证据
这表明,浸润性癌症可能在没有长时间且可检测到的癌前阶段就开始了。此外,
增生性病变并没有明确的进展,这表明许多早期癌症被过度治疗。
尽管观察到早期发现的数量急剧增加,致命性疾病的死亡率也出现了类似的大幅下降
尚未观察到转移性疾病。一些人甚至认为,许多筛查发现的早期病变
自发地解决或倒退。相比之下,最致命的癌症事先逃脱了检测和转移
为了侦测。
假设:我们假设癌症的进展,就像正常组织的动态平衡一样,是随机的和受控的
以定义空间和微环境约束。
具体目标:目标1.明确乳腺癌进展的动态平衡原理
HER2+乳腺癌小鼠模型的建立。目的2.剖析HER2亚型在转移级联反应中的作用
乳房肿瘤。
研究设计/方法:在这里,我们将使用一个经过验证的癌症彩虹建模系统来可视化和
分析体内肿瘤的生长速度。最先进的多光子实时成像将用于成像和量化
乳腺内肿瘤的时空进展潜能与微环境特征
(ECM、巨噬细胞、血管)。超过8周的纵向成像将捕捉到肿瘤的比率
免疫功能正常的小鼠体内浸润性乳腺癌的进展和起源。
相关性:60多年前,外科肿瘤学家试图解释为什么更早的手术干预
并没有改善乳腺癌的存活率,假设肿瘤和宿主之间的适应设定了
一种浸润性癌症在确诊前多年的轨迹。支持者认为,形成期的早期
肿瘤-TME的适应性已经注定了一些肿瘤变得侵袭性和致命性。此外,还有许多
乳腺癌的病变实际上可能会退化,这表明癌症的进展可能是随机的。新颖的成像技术
需要模式和复杂的肿瘤谱系训练策略来解决这一具有挑战性的问题。我们的
肿瘤过程中利用小鼠模型和高分辨率纵向成像的实验研究
进展将决定癌症进展是否是确定性的,这将为
了解乳腺癌的进展情况。
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 }}
Jose Javier Bravo-Cordero其他文献
Jose Javier Bravo-Cordero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('Jose Javier Bravo-Cordero', 18)}}的其他基金
IMAT-ITCR Collaboration: Artificial intelligence enhanced breast cancer dormancy cell classification-based organelle-morphology and topology
IMAT-ITCR 合作:人工智能增强乳腺癌休眠细胞分类的细胞器形态和拓扑
- 批准号:
10884760 - 财政年份:2023
- 资助金额:
$ 9.98万 - 项目类别:
Intersectional genetics-based biosensors for dormant cancer cells
基于交叉遗传学的休眠癌细胞生物传感器
- 批准号:
10612300 - 财政年份:2023
- 资助金额:
$ 9.98万 - 项目类别:
Recording the natural history of cancer progression using a Crainbow model of HER2+ cancer
使用 HER2 癌症的 Crainbow 模型记录癌症进展的自然史
- 批准号:
10630320 - 财政年份:2022
- 资助金额:
$ 9.98万 - 项目类别:
Defining the role of type III collagen and the collagen-binding receptor DDR1 in metastatic dormancy
定义 III 型胶原和胶原结合受体 DDR1 在转移休眠中的作用
- 批准号:
10263927 - 财政年份:2020
- 资助金额:
$ 9.98万 - 项目类别:
Defining the role of type III collagen and the collagen-binding receptor DDR1 in metastatic dormancy
定义 III 型胶原和胶原结合受体 DDR1 在转移休眠中的作用
- 批准号:
10439836 - 财政年份:2020
- 资助金额:
$ 9.98万 - 项目类别:
Defining the role of type III collagen and the collagen-binding receptor DDR1 in metastatic dormancy
定义 III 型胶原和胶原结合受体 DDR1 在转移休眠中的作用
- 批准号:
10653992 - 财政年份:2020
- 资助金额:
$ 9.98万 - 项目类别:
Protrusion plasticity during in vivo tumor cell migration
体内肿瘤细胞迁移过程中的突出可塑性
- 批准号:
9321473 - 财政年份:2016
- 资助金额:
$ 9.98万 - 项目类别:
Protrusion plasticity during in vivo tumor cell migration
体内肿瘤细胞迁移过程中的突出可塑性
- 批准号:
9534544 - 财政年份:2016
- 资助金额:
$ 9.98万 - 项目类别:
相似国自然基金
greenwashing behavior in China:Basedon an integrated view of reconfiguration of environmental authority and decoupling logic
- 批准号:
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金项目
相似海外基金
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
- 批准号:
2876993 - 财政年份:2027
- 资助金额:
$ 9.98万 - 项目类别:
Studentship
Collaborative Research: Chain Transform Fault: Understanding the dynamic behavior of a slow-slipping oceanic transform system
合作研究:链变换断层:了解慢滑海洋变换系统的动态行为
- 批准号:
2318855 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Continuing Grant
Collaborative Research: Subduction Megathrust Rheology: The Combined Roles of On- and Off-Fault Processes in Controlling Fault Slip Behavior
合作研究:俯冲巨型逆断层流变学:断层上和断层外过程在控制断层滑动行为中的综合作用
- 批准号:
2319848 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Standard Grant
Collaborative Research: Subduction Megathrust Rheology: The Combined Roles of On- and Off-Fault Processes in Controlling Fault Slip Behavior
合作研究:俯冲巨型逆断层流变学:断层上和断层外过程在控制断层滑动行为中的综合作用
- 批准号:
2319849 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Standard Grant
MCA Pilot PUI: From glomeruli to pollination: vertical integration of neural encoding through ecologically-relevant behavior
MCA Pilot PUI:从肾小球到授粉:通过生态相关行为进行神经编码的垂直整合
- 批准号:
2322310 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Continuing Grant
CAREER: A cortex-basal forebrain loop enabling task-specific cognitive behavior
职业:皮层基底前脑环路实现特定任务的认知行为
- 批准号:
2337351 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Continuing Grant
Conference: 2024 Photosensory Receptors and Signal Transduction GRC/GRS: Light-Dependent Molecular Mechanism, Cellular Response and Organismal Behavior
会议:2024光敏受体和信号转导GRC/GRS:光依赖性分子机制、细胞反应和生物体行为
- 批准号:
2402252 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Standard Grant
Nanoscopic elucidation of dynamic behavior of RNA viral nucleocapsid proteins using high-speed atomic force microscopy (HS-AFM)
使用高速原子力显微镜 (HS-AFM) 纳米级阐明 RNA 病毒核衣壳蛋白的动态行为
- 批准号:
24K18449 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
ERI: Data-Driven Analysis and Dynamic Modeling of Residential Power Demand Behavior: Using Long-Term Real-World Data from Rural Electric Systems
ERI:住宅电力需求行为的数据驱动分析和动态建模:使用农村电力系统的长期真实数据
- 批准号:
2301411 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Standard Grant
Understanding the synthesis and electronic behavior of beta tungsten thin film materials
了解β钨薄膜材料的合成和电子行为
- 批准号:
23K20274 - 财政年份:2024
- 资助金额:
$ 9.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)