Novel strategies to target lung cancer metastasis to bone
针对肺癌骨转移的新策略
基本信息
- 批准号:10513138
- 负责人:
- 金额:$ 21.95万
- 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:2022-06-15 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:A549AdenocarcinomaAdenocarcinoma In SituAllelesAntibodiesBehaviorBreastCalciumCancer Cell GrowthCancer ControlCancer EtiologyCancer ModelCancer PatientCause of DeathCell LineCell SurvivalCellsClinicalComplexConsumptionDataDiagnosisDietDietary InterventionDiseaseDisseminated Malignant NeoplasmElementsEnvironmentEtiologyEventFailureFractureFrequenciesGenetically Engineered MouseGrowthHomingHyperplasiaImageImmune systemIncidenceIntakeKRASG12DKnowledgeLinkLoxP-flanked alleleLuciferasesLungLung AdenocarcinomaMalignant NeoplasmsMalignant neoplasm of lungMetastatic Neoplasm to the BoneMethodologyMicroscopyMineralsModalityModelingMonitorMusNeoplasm MetastasisNutritionalOsteoporosisPainPharmaceutical PreparationsPharmacologyPhenotypePhosphotransferasesPhysiologicalPre-Clinical ModelPrevalencePreventionPrevention approachProcessPrognosisProstateRegulationResolutionRisk FactorsSerumSiteSkeletonSoilTNFSF11 geneTestingTherapeuticTherapeutic StudiesTransgenic MiceTropismTumor Suppressor ProteinsXenograft Modelbasebisphosphonatebonebone imagingbone lossbone metabolismbone turnovercancer cellcancer diagnosiscancer preventioncell behaviorcellular imagingcomorbiditydraining lymph nodedrug repurposingfracture riskhuman migrationimaging modalityin vivoinnovationinorganic phosphateinsightlanthanum carbonatelifestyle factorsmetastatic processmicroCTmouse modelneoplastic cellnovelnovel anticancer drugnovel strategiesnovel therapeutic interventionnutritionosteopontinpain reductionpre-clinicalpreventrelease factorsensorside effectskeletaltherapeutic targetthree dimensional cell culturetumortumor progression
项目摘要
Project Summary/Abstract:
Metastasis is the leading cause of death from cancer. Metastasis to bone represents a particularly poor
prognosis. Unfortunately, the skeleton is one of the most common sites of metastasis for cancers such as
breast, prostate and lung. Further, metastasis to bone results in significant pain, loss of mobility and increased
fractures, among other comorbidities. The underlying mechanisms are incompletely understood and treatment
options are mostly limited to attempting to reduce pain and fracture risk after diagnosis. Therefore, an
enhanced understanding of the underlying etiology and/or a novel strategy to prevent or reduce bone
metastasis would represent a significant advance to a field sorely in need of new options. One major obstacle
to understanding, as well as developing therapeutic options for bone metastases is the paucity of pre-clinical
models that faithfully recapitulate this multi-stage complex process. We have identified a novel genetically
engineered mouse model in which to study lung cancer progression and metastasis to bone. Further, we
believe we have identified a novel risk factor for cancer cell growth and survival as well as a factor that strongly
influences the bone microenvironment in inorganic phosphate (Pi). Studies proposed herein will probe at the
underlying mechanisms of bone metastasis combining a state-of-the-art mouse metastasis model, advanced
microscopy and micro-computed tomography in the context of a novel and highly translational nutrition based
prevention approach. Specifically, we will test the hypothesis that: The KrasG12D; Lkb1fl/fl; Rosa-luciferase
mouse represents a model of spontaneous lung cancer metastasis to bone. Further, that this model can be
used to study therapeutic and prevention modalities as well as provide mechanistic insight into this complex
disease. To test this hypothesis we will: 1) therapeutically target spontaneous metastasis to bone using the
KLLlenti mouse model, and 2) determine if differences in Pi transport drive a bone seeking phenotype. Impact:
Results from the current proposal have the potential to provide new information about the mechanisms by
which a common nutritional element might be manipulated to alter cell behavior related to cancer etiology as
well as a better understanding of the skeletal environment which promotes tumor cell establishment.
项目概要/摘要:
转移是癌症死亡的主要原因。骨转移是一种特别差的
预后不幸的是,骨骼是癌症最常见的转移部位之一,
乳腺前列腺和肺此外,转移到骨导致显著的疼痛、移动性丧失和增加的疼痛。
骨折和其他合并症。其潜在机制尚未完全了解,
选择大多局限于试图减少诊断后的疼痛和骨折风险。所以一间
增强对潜在病因学的理解和/或预防或减少骨质疏松的新策略
转移将代表着一个迫切需要新选择的领域的重大进展。一个主要障碍
了解,以及开发骨转移的治疗选择是缺乏临床前
模型忠实地概括了这个多阶段的复杂过程。我们从基因上鉴定出一种新的
研究肺癌进展和骨转移的工程小鼠模型。我们还
我相信我们已经确定了一个新的癌细胞生长和存活的风险因素,以及一个强烈影响癌细胞生长和存活的因素。
无机磷(Pi)影响骨微环境。本文提出的研究将探讨
骨转移的潜在机制结合最先进的小鼠转移模型,
显微镜和微型计算机断层扫描的背景下,一种新的和高度翻译的营养为基础的
预防方法。具体而言,我们将检验以下假设:KrasG 12 D; Lkb 1fl/fl; Rosa-荧光素酶
小鼠代表自发性肺癌转移到骨的模型。此外,该模型可以
用于研究治疗和预防模式,并提供对这种复杂的机制的见解,
疾病为了验证这一假设,我们将:1)使用免疫组织化学方法治疗性靶向自发转移至骨。
KLLlenti小鼠模型,和2)确定Pi转运的差异是否驱动骨寻求表型。影响:
目前提案的结果有可能提供有关机制的新信息,
其中一种常见的营养元素可能被操纵以改变与癌症病因学相关的细胞行为,
以及更好地了解促进肿瘤细胞建立的骨骼环境。
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 }}
GEORGE R. BECK其他文献
GEORGE R. BECK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('GEORGE R. BECK', 18)}}的其他基金
Novel strategies to target lung cancer metastasis to bone
针对肺癌骨转移的新策略
- 批准号:
10646351 - 财政年份:2022
- 资助金额:
$ 21.95万 - 项目类别:
ShEEP Request For A Pre-Clinical In-Vivo X-Ray Micro Computed-Tomography Scanner
ShEEP 请求临床前体内 X 射线微型计算机断层扫描仪
- 批准号:
10178581 - 财政年份:2020
- 资助金额:
$ 21.95万 - 项目类别:
Bio-active Nanoparticles and the stimulation of autophagy for improved bone mass
生物活性纳米颗粒和刺激自噬以改善骨量
- 批准号:
9280823 - 财政年份:2014
- 资助金额:
$ 21.95万 - 项目类别:
Bio-active Nanoparticles and the stimulation of autophagy for improved bone mass
生物活性纳米颗粒和刺激自噬以改善骨量
- 批准号:
8974367 - 财政年份:2014
- 资助金额:
$ 21.95万 - 项目类别:
Bio-active Nanoparticles and the stimulation of autophagy for improved bone mass
生物活性纳米颗粒和刺激自噬以改善骨量
- 批准号:
8634211 - 财政年份:2014
- 资助金额:
$ 21.95万 - 项目类别:
Contribution of Phosphate to Inflammatory Bone Loss
磷酸盐对炎性骨质流失的影响
- 批准号:
10588936 - 财政年份:2013
- 资助金额:
$ 21.95万 - 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
- 批准号:
8444660 - 财政年份:2010
- 资助金额:
$ 21.95万 - 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
- 批准号:
7889954 - 财政年份:2010
- 资助金额:
$ 21.95万 - 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
- 批准号:
8076343 - 财政年份:2010
- 资助金额:
$ 21.95万 - 项目类别:
Inorganic phosphate regulated proliferation, transformation and tumorigenesis
无机磷酸盐调节增殖、转化和肿瘤发生
- 批准号:
8240098 - 财政年份:2010
- 资助金额:
$ 21.95万 - 项目类别:
相似国自然基金
大肠癌发生机制的adenoma-adenocarcinoma pathway同serrated pathway的关系的研究
- 批准号:30840003
- 批准年份:2008
- 资助金额:12.0 万元
- 项目类别:专项基金项目
相似海外基金
Synergistic Radiosensitization of Hypoxic Pancreatic Adenocarcinoma using Gd-Texaphyrin Oxygen-Loaded Nanodroplets
使用 Gd-Texaphyrin 载氧纳米液滴对缺氧胰腺腺癌进行协同放射增敏
- 批准号:
478914 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Operating Grants
Expression mechanism of immune checkpoint molecules after carbon-ion radiotherapy in cervical adenocarcinoma specimens
宫颈腺癌碳离子放疗后免疫检查点分子的表达机制
- 批准号:
23K14913 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Study of fibrosis in pancreatic ductal adenocarcinoma (PDAC) and application of adipose-derived stromal/stem cells for PDAC treatment
胰腺导管腺癌(PDAC)纤维化的研究以及脂肪源性基质/干细胞在 PDAC 治疗中的应用
- 批准号:
23K15035 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
IRAK4 AS A NOVEL IMMUNOTHERAPEUTIC TARGET IN PANCREATIC DUCTAL ADENOCARCINOMA
IRAK4 作为胰腺导管腺癌的新型免疫治疗靶点
- 批准号:
10442874 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Therapeutic Targeting of NSD2 in Lung Adenocarcinoma
NSD2 在肺腺癌中的治疗靶向
- 批准号:
10657069 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Control mechanisms of lung adenocarcinoma by SGLT2 inhibitors for treating diabetes mellitus.
SGLT2抑制剂治疗糖尿病对肺腺癌的控制机制。
- 批准号:
23K08326 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Establishment of histological transformation model from lung small cell carcinoma from adenocarcinoma to explore the therapeutic strategies of small cell lung carcinoma.
建立肺小细胞癌腺癌组织学转化模型,探讨小细胞肺癌的治疗策略。
- 批准号:
23K14614 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms of tumor progression controlled by tumor-initiating cells and cancer-associated fibroblasts in pancreatic adenocarcinoma.
阐明胰腺腺癌中肿瘤起始细胞和癌症相关成纤维细胞控制的肿瘤进展机制。
- 批准号:
23K15075 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Molecular mechanisms for development of pulmonary invasive mucinous adenocarcinoma
肺浸润性粘液腺癌发生的分子机制
- 批准号:
23H02698 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidating the Cellular Origins of lung adenocarcinoma
阐明肺腺癌的细胞起源
- 批准号:
10743611 - 财政年份:2023
- 资助金额:
$ 21.95万 - 项目类别: