Targeting lymph node metastases to prevent cancer progression
针对淋巴结转移以预防癌症进展
基本信息
- 批准号:10542290
- 负责人:
- 金额:$ 6.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-02 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdministrative SupplementAnimal ModelAntigensBiologicalBlood VesselsCancer PatientCell LineClinicalComplexDataDiseaseDisease ProgressionDisseminated Malignant NeoplasmDistantDistant MetastasisElementsEquipmentGoalsGrowthHomeImmuneImmune responseImmune systemImmunology procedureImmunosuppressionKnowledgeLaboratoriesLymphatic MetastasisLymphatic SystemMalignant Lymph Node NeoplasmMetastatic Neoplasm to Lymph NodesMolecularNeoplasm MetastasisOperative Surgical ProceduresPatient-Focused OutcomesPatientsPlayPositioning AttributeProcessPrognosisRecommendationRegimenReticular CellRiskRoleSiteSurvival RateSystemSystemic TherapyTestingTherapeuticTranslatingTumor ImmunityWorkangiogenesisanti-tumor immune responsecancer cellimprovedinnovationintravital imagingintravital microscopylymph nodesnovel therapeutic interventionnovel therapeuticspreventprognostic indicatortumor progression
项目摘要
This administrative supplement will support the completion of the current Aims of R01CA214913. Completing
the current Aims will also provide preliminary data to respond to the Summary Statement of the A0 renewal
application. These preliminary data will strengthen the A1 submission of the renewal application. Breakthroughs
in our knowledge of the molecular and cellular mechanisms regulating metastasis have yet to be broadly
translated into improved survival rates for patients with metastatic disease. Lymph node metastasis in a cancer
patient brings with it a poorer prognosis and the recommendation for systemic therapy. However, it is unclear
whether lymphatic metastases are only predictive or whether they play a role in cancer progression and the
emergence of distant metastases. Evidence shows that treating lymph node metastases improves survival in
some patients. The work proposed here aims to build a biological understanding of lymph node metastases in
order to define their role in disease progression and identify new therapeutic interventions to improve patient
survival. Recently, we have shown that lymph node metastases do not require angiogenesis to grow and do not
respond to anti-angiogenic therapy. We will build upon our unique expertise by addressing why lymph node
metastasis are such strong prognostic indicators and explore how lymph node metastasis drive cancer
progression. Specifically, we will test the hypotheses that lymph node metastases disseminate to distant sites
(Aim 1) and inhibit the ability of the immune system to develop and maintain anti-tumor immunity (Aim 2). We
will accomplish our goals using innovative animal models that allow state-of-the-art intravital microscopy of
spontaneous lymph node metastasis. In Aim 1, we will determine whether cancer cells utilize the fibroblastic
reticular cell-lined conduit system in lymph nodes to home to blood vessels and spread to distant sites. We will
attempt to block this process. In Aim 2, we will determine whether metastatic lymph nodes retain the ability to
initiate immune responses to new antigens. Further, we will determine the mechanism of immune suppression
in metastatic lymph nodes. We will attempt to increase immune effector function in lymph node metastases to
eradicate lymph node disease and stimulate systemic anti-tumor immunity. In completing these aims, we will
have better lymph node focused therapeutic options to limit the growth and spread of cancer from lymph nodes
and thus provide better outcomes for patients. Dr. Padera is an expert in intravital microscopy of the lymphatic
system and mechanisms of lymph node metastasis. Critical elements to achieving these goals are intravital
imaging equipment, complex animal models and functional immunological assays, all available in the PI’s
laboratory. In addition, the assembled team has complementary expertise that will enable them to overcome any
problems that occur during the project, uniquely positioning us to address these clinically driven questions. With
the completion of our studies, we will be able to better contain and eradicate lymph node metastasis to extend
survival for patients with metastatic cancer.
本行政补充将支持完成R01CA214913的当前目标。完成
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multiphoton Phosphorescence Quenching Microscopy Reveals Kinetics of Tumor Oxygenation during Antiangiogenesis and Angiotensin Signaling Inhibition.
- DOI:10.1158/1078-0432.ccr-22-0486
- 发表时间:2022-07-15
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Progression of Metastasis through Lymphatic System.
- DOI:10.3390/cells10030627
- 发表时间:2021-03-12
- 期刊:
- 影响因子:6
- 作者:Zhou H;Lei PJ;Padera TP
- 通讯作者:Padera TP
Fate Mapping of Cancer Cells in Metastatic Lymph Nodes Using Photoconvertible Proteins.
- DOI:10.1007/978-1-0716-1205-7_26
- 发表时间:2021
- 期刊:
- 影响因子:0
- 作者:Pereira ER;Kedrin D;Padera TP
- 通讯作者:Padera TP
Regeneration of collecting lymphatic vessels following injury.
损伤后集合淋巴管的再生。
- DOI:10.21203/rs.3.rs-3025656/v1
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Razavi,MohammadS;Lei,Pin-Ji;Amoozgar,Zohreh;Leartprapun,Nichaluk;Nadkarni,SeemantiniK;Baish,JamesW;Padera,TimothyP;Munn,LanceL
- 通讯作者:Munn,LanceL
Inducible Nitric Oxide Synthase and CD11b+Gr1+ Cells Impair Lymphatic Contraction of Tumor-Draining Lymphatic Vessels.
诱导型一氧化氮合酶和 CD11b Gr1 细胞会损害肿瘤引流淋巴管的淋巴收缩。
- DOI:10.1089/lrb.2018.0013
- 发表时间:2019
- 期刊:
- 影响因子:1.4
- 作者:Liao,Shan;Bouta,EchoeM;Morris,LindaM;Jones,Dennis;Jain,RakeshK;Padera,TimothyP
- 通讯作者:Padera,TimothyP
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TIMOTHY P PADERA其他文献
TIMOTHY P PADERA的其他文献
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{{ truncateString('TIMOTHY P PADERA', 18)}}的其他基金
Targeting lymph node metastases to block cancer progression
针对淋巴结转移阻止癌症进展
- 批准号:
10743193 - 财政年份:2023
- 资助金额:
$ 6.94万 - 项目类别:
Reversing aging-induced lymphatic dysfunction to improve immune function
逆转衰老引起的淋巴功能障碍,改善免疫功能
- 批准号:
10371505 - 财政年份:2022
- 资助金额:
$ 6.94万 - 项目类别:
Reversing aging-induced lymphatic dysfunction to improve immune function
逆转衰老引起的淋巴功能障碍,改善免疫功能
- 批准号:
10544735 - 财政年份:2022
- 资助金额:
$ 6.94万 - 项目类别:
Targeting lymph node metastases to prevent cancer progression
针对淋巴结转移预防癌症进展
- 批准号:
9286149 - 财政年份:2017
- 资助金额:
$ 6.94万 - 项目类别:
Characterization of lymphatic contraction during infection
感染期间淋巴收缩的特征
- 批准号:
8422972 - 财政年份:2012
- 资助金额:
$ 6.94万 - 项目类别:
Characterization of lymphatic contraction during infection
感染期间淋巴收缩的特征
- 批准号:
8225628 - 财政年份:2012
- 资助金额:
$ 6.94万 - 项目类别:
Characterizing lymphatic micrometastases: prognostic and therapeutic implications
淋巴微转移的特征:预后和治疗意义
- 批准号:
8146385 - 财政年份:2011
- 资助金额:
$ 6.94万 - 项目类别:
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