NF-kB Regulation of the Muscle Microenvironment in Cancer Cachexia
NF-kB 对癌症恶病质肌肉微环境的调节
基本信息
- 批准号:10576873
- 负责人:
- 金额:$ 50.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-26 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:Adipose tissueAnabolismAndrogen TherapyAnti-Inflammatory AgentsAppetite StimulantsAreaAtrophicBackBody WeightBody Weight decreasedCachexiaCatabolismCellsCessation of lifeChronic DiseaseChronic Kidney FailureChronic Obstructive Pulmonary DiseaseClinicDataDiseaseEventFatigueFatty acid glycerol estersGDF8 geneGoalsHeart failureImmuneInflammationInflammatoryLaboratoriesLinkMacrophageMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of pancreasMorbidity - disease rateMusMuscleMuscle ProteinsMuscle satellite cellMuscular AtrophyMyoblastsNF-kappa BNatural regenerationOperative Surgical ProceduresPatientsPhase III Clinical TrialsPhenotypePrevalenceProcessProductionProteinsRadiation therapyRegulationResearchRheumatoid ArthritisRoleSamplingSarcolemmaSignal TransductionSkeletal MuscleSyndromeTestingTherapeuticTranslatingWeightbench to bedsidecancer cachexiacancer carechemokinechemotherapycombatcytokineeffective therapyfrailtyimprovedinflammatory milieuinsightmortalitymuscle formnovel therapeuticspancreatic cancer patientsphase II trialpreventprimary endpointprogramsrecruitrepairedresponseskeletal muscle wastingstem cellstherapeutic targettumorwasting
项目摘要
ABSTRACT
Cachexia is a debilitating syndrome that results in severe, involuntary weight loss due to the depletion of
skeletal muscle mass. This syndrome occurs in a majority of cancers and contributes to approximately a third
of all cancer deaths. Currently, no effective therapy exists to combat this malignant disorder. For pancreatic
cancer the potential benefit for effective cachexia therapies may be even greater than for other cachexia
associated malignancies, since 90% of these patients lose on average 14% of their pre-illness weight, and
cachexia dramatically limits their ability to tolerate surgery, chemo- or radiotherapy. New therapies will likely
evolve from an enhanced understanding of the mechanisms leading to muscle wasting. Our recent efforts have
focused on events that occur outside the myofiber in the muscle microenvironment. We showed that circulating
tumor factors induce skeletal muscle damage leading to the activation of NF-kB in muscle progenitor cells that
associated with an engaged regeneration program. However, regeneration is inhibited leading to muscle
atrophy. We now find that NF-kB activation in muscle stem cells also promotes a local muscle inflammation,
characterized by the production of cytokines and chemokines. These signals promote the recruitment of
macrophages expressing M1 inflammatory and M2 anti-inflammatory makers. The goal of this application is to
test the hypothesis that NF-kB in muscle progenitor cells regulates this local inflammatory environment that
contributes to muscle atrophy. Towards this goal we seek to perform the following two specific aims: 1)
Determine how NF-kB regulates local muscle inflammation in cancer cachexia; and 2) Elucidate the phenotype
and relevance of macrophages in cancer-induced muscle wasting. Achieving this goal will not only provide
insight into the mechanisms and therapeutic targets of muscle wasting in cancer, but will also broaden an area
of cachexia research that is currently underexplored.
摘要
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 }}
Denis C Guttridge其他文献
Denis C Guttridge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('Denis C Guttridge', 18)}}的其他基金
Project 2 NF-#B regulation in muscle wasting and pancreatic cancer-induced cachexia
项目2 NF-
- 批准号:
10172470 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
The role of the macroenvironment in pancreatic cancer-induced cachexia
大环境在胰腺癌引起的恶病质中的作用
- 批准号:
10441210 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
The role of the macroenvironment in pancreatic cancer-induced cachexia
大环境在胰腺癌引起的恶病质中的作用
- 批准号:
10172468 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
Project 2 NF-#B regulation in muscle wasting and pancreatic cancer-induced cachexia
项目2 NF-
- 批准号:
10634576 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
Project 2 NF-#B regulation in muscle wasting and pancreatic cancer-induced cachexia
项目2 NF-
- 批准号:
10441213 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
The role of the macroenvironment in pancreatic cancer-induced cachexia
大环境在胰腺癌引起的恶病质中的作用
- 批准号:
10634573 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
NF-kB Regulation of the Muscle Microenvironment in Cancer Cachexia
NF-kB 对癌症恶病质肌肉微环境的调节
- 批准号:
10359196 - 财政年份:2020
- 资助金额:
$ 50.48万 - 项目类别:
相似海外基金
Bone-Adipose Interactions During Skeletal Anabolism
骨骼合成代谢过程中骨-脂肪相互作用
- 批准号:
10590611 - 财政年份:2022
- 资助金额:
$ 50.48万 - 项目类别:
Bone-Adipose Interactions During Skeletal Anabolism
骨骼合成代谢过程中的骨-脂肪相互作用
- 批准号:
10706006 - 财政年份:2022
- 资助金额:
$ 50.48万 - 项目类别:
Bone-Adipose Interactions During Skeletal Anabolism
骨骼合成代谢过程中骨-脂肪相互作用
- 批准号:
10368975 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
BCCMA: Foundational Research to Act Upon and Resist Conditions Unfavorable to Bone (FRACTURE CURB): Combined long-acting PTH and calcimimetics actions on skeletal anabolism
BCCMA:针对和抵抗不利于骨骼的条件的基础研究(遏制骨折):长效 PTH 和拟钙剂联合作用对骨骼合成代谢的作用
- 批准号:
10365254 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
Bone-Adipose Interactions During Skeletal Anabolism
骨骼合成代谢过程中骨-脂肪相互作用
- 批准号:
10202896 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
BCCMA: Foundational Research to Act Upon and Resist Conditions Unfavorable to Bone (FRACTURE CURB): Combined long-acting PTH and calcimimetics actions on skeletal anabolism
BCCMA:针对和抵抗不利于骨骼的条件的基础研究(遏制骨折):长效 PTH 和拟钙剂联合作用对骨骼合成代谢的作用
- 批准号:
10531570 - 财政年份:2021
- 资助金额:
$ 50.48万 - 项目类别:
Dissecting molecular mechanisms implicated in age- and osteoarthritis-related decline in anabolism in articular cartilage
剖析与年龄和骨关节炎相关的关节软骨合成代谢下降有关的分子机制
- 批准号:
10541847 - 财政年份:2019
- 资助金额:
$ 50.48万 - 项目类别:
Dissecting molecular mechanisms implicated in age- and osteoarthritis-related decline in anabolism in articular cartilage
剖析与年龄和骨关节炎相关的关节软骨合成代谢下降有关的分子机制
- 批准号:
10319573 - 财政年份:2019
- 资助金额:
$ 50.48万 - 项目类别:
Dissecting molecular mechanisms implicated in age- and osteoarthritis-related decline in anabolism in articular cartilage
剖析与年龄和骨关节炎相关的关节软骨合成代谢下降有关的分子机制
- 批准号:
10062790 - 财政年份:2019
- 资助金额:
$ 50.48万 - 项目类别:
Promotion of NAD+ anabolism to promote lifespan
促进NAD合成代谢以延长寿命
- 批准号:
DE170100628 - 财政年份:2017
- 资助金额:
$ 50.48万 - 项目类别:
Discovery Early Career Researcher Award