Role of epidermis in regulating inflammatory skin manifestations of post-surgical lymphedema
表皮在调节术后淋巴水肿炎症性皮肤表现中的作用
基本信息
- 批准号:10606927
- 负责人:
- 金额:$ 23.36万
- 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:2022-12-21 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AcidityAlkalinizationAmericanAnimal ModelAntibioticsAtopic DermatitisBiopsyCD4 Positive T LymphocytesCellsChronicClinicalDeformityDepositionDermisDeveloped CountriesDevelopmentDiseaseDisease ProgressionEpidermisFunctional disorderGoalsGynecologicHigh PrevalenceHistologicHospitalizationImmune responseImpairmentInfectious Skin DiseasesInfiltrationInflammationInflammatoryInflammatory ResponseInjuryIntravenousKininogenaseKnowledgeLymphaticLymphedemaMediatingMediatorMethodsMusOutcomePAR-2 ReceptorPainPalliative CarePathologicPathologyPathway interactionsPatientsPeptide HydrolasesPharmaceutical PreparationsPhase I Clinical TrialsPhysical therapyPlayPositioning AttributePre-Clinical ModelPreventionProteinsQuality of lifeReactionRecurrenceRiskRoleSerine ProteaseSerine Proteinase InhibitorsSeverity of illnessSignal PathwaySkinSkin AbnormalitiesSkin ManifestationsSolid NeoplasmStainsStratum corneumSurgical complicationSwellingT-LymphocyteTSLP geneTestingTissuesUpper ExtremityUrologic Cancerbreast surgerycancer complicationcancer therapychronic inflammatory skincytokineeffective therapyfunctional disabilityiatrogenic injuryimprovedinhibiting antibodyinnovationkeratinocytelaboratory experienceloss of functionlymphatic pumplymphatic vesselmalignant breast neoplasmmelanomamouse modelnovelpalliativepreventrecurrent infectionreduce symptomsresponsesarcomasecondary lymphedemaskin barrierskin disordersymptom treatmenttumorurologic
项目摘要
PROJECT SUMMARY/ABSTRACT
Secondary lymphedema is a common and dreaded disease that occurs in patients treated for a variety
of solid tumors. An estimated 20–40% of Americans treated surgically for breast cancer, melanoma,
gynecological or urologic tumors go on to develop lymphedema. Once the disease develops, it is usually
progressive and causes significant functional impairment, recurrent infections, and decreased quality of life.
Current treatments are palliative, aiming to treat symptoms and prevent progression rather than cure the
underlying anatomic abnormalities. Thus, development of novel treatments for this disease is an important
goal.
Recent studies have shown that infiltration of T helper 2 (Th2)-differentiated CD4+ cells is an important
mediator of lymphedema development by regulating fibroadipose tissue deposition, preventing formation of
collateral lymphatics, decreasing lymphatic pumping, and causing lymphatic leakiness/dysfunction. However,
the cellular mechanisms that activate these Th2 inflammatory responses remain unknown. In preliminary
studies, we have found that the epidermis may play an important role in regulating Th2 inflammatory
responses in lymphedema. For example, we have found that the expression of Th2-inducing cytokines—
cytokines known to coordinate Th2 inflammation in other chronic skin disorders—is significantly increased by
keratinocytes in lymphedematous tissues of patients with unilateral upper extremity lymphedema. We have
also found that the expression of serine proteases, an important mechanism regulating Th2-inducing cytokine
expression in other skin disorders, is also increased. Using mouse models, we have found that epidermal
changes, including decreased expression of skin barrier proteins and of Th2-inducing cytokines, precedes
infiltration of Th2 differentiated CD4+ cells. Based on these preliminary studies, as well as the pathophysiology
of other Th2-mediated chronic skin disorders, we will test the hypothesis that impaired skin barrier function and
skin pH regulate the expression of Th2-inducing cytokines by keratinocytes following lymphatic injury. Our
study is innovative because the role of the epidermis has not been elucidated. This gap in our knowledge is
important as epidermal changes are a prominent finding in lymphedema. We will test our hypothesis by
analyzing skin barrier function, pH, and Th2-inducing cytokine expression in patients with unilateral breast
cancer-related lymphedema. In other studies, we will use animal models to analyze the cellular mechanisms
that regulate epidermal Th2-inducing cytokine expression and how these changes regulate the
pathophysiology of lymphedema.
项目总结/文摘
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)
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Babak J Mehrara其他文献
Babak J Mehrara的其他文献
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{{ truncateString('Babak J Mehrara', 18)}}的其他基金
Molecular mechanisms of age-related lymphatic dysfunction
年龄相关淋巴功能障碍的分子机制
- 批准号:
10538995 - 财政年份:2022
- 资助金额:
$ 23.36万 - 项目类别:
Molecular mechanisms of age-related lymphatic dysfunction
年龄相关淋巴功能障碍的分子机制
- 批准号:
10665795 - 财政年份:2022
- 资助金额:
$ 23.36万 - 项目类别:
Restoration of lymphatic function in postsurgical lymphedema with lymph node transfer
通过淋巴结转移恢复术后淋巴水肿的淋巴功能
- 批准号:
9185953 - 财政年份:2015
- 资助金额:
$ 23.36万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
8532029 - 财政年份:2012
- 资助金额:
$ 23.36万 - 项目类别:
Mechanisms of fibrosis in post-surgical lymphedema
术后淋巴水肿纤维化的机制
- 批准号:
10063531 - 财政年份:2012
- 资助金额:
$ 23.36万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
8372995 - 财政年份:2012
- 资助金额:
$ 23.36万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
8695460 - 财政年份:2012
- 资助金额:
$ 23.36万 - 项目类别:
Mechanisms of fibrosis and lymphatic dysfunction in post-surgical lymphedema
术后淋巴水肿纤维化和淋巴功能障碍的机制
- 批准号:
9094645 - 财政年份:2012
- 资助金额:
$ 23.36万 - 项目类别:
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