Mitigation of lymphatic injury by retinoic acid therapyin a large animal model
Mitigation of lymphatic injury by retinoic acid therapyin a large animal model
批准号:
10452437
负责人:
Alex K. Wong
金额:
$8.8万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-07-01 至 2023-06-30
关键词:
AddressAdipose tissueAffectAmericanAnatomyAnimal ModelAnimalsBenefits and RisksBreastCharacteristicsChronicClinicalDataDelayed-Action PreparationsDepositionDermalDevelopmentDiseaseDisease ProgressionDistantDoseDrug Delivery SystemsDyesEczemaExcisionFDA approvedFamily suidaeFibrosisFunctional disorderGene ExpressionGenesGoalsGrowth FactorHGF geneHindlimbHumanImmune System DiseasesIn VitroIncidenceIndividualIndocyanine GreenInfectionInflammationInflammatory InfiltrateInjuryLaboratoriesLimb structureLymph Node DissectionsLymph Node MappingLymphangiogenesisLymphaticLymphatic ObstructionLymphatic functionLymphedemaLymphoid TissueMagnetic Resonance ImagingMalignant NeoplasmsMeasuresMediatingModelingMolecularMusNatural regenerationObstructionOperative Surgical ProceduresOralPelvic CancerPelvisPharmacologyPharmacology StudyPhysiologicalPhysiologyPrevention approachQuality of lifeRecurrenceRefractoryResidual TumorsRiskRodentRodent ModelRouteSafetySeriesSiteSkin Kaposi&aposs SarcomaSkin TissueSpecificityStructureSurgical InjuriesSwellingTailTechniquesTeratogensTherapeuticThree-Dimensional ImagingTimeTissuesTranslatingTraumaTretinoinUnited StatesUrogenital CancerVascular Endothelial Growth Factor Calitretinoinbaseclinical translationclinically relevantdesigndisabilitydrug metabolismfollow-upimprovedin vivointraperitoneallymph nodeslymphatic circulationlymphatic vesselmalignant breast neoplasmmouse modelneoplastic cellnovel therapeuticsporcine modelpre-clinicalpreservationpreventsecondary lymphedemaskin lesionsoft tissuetranslation to humanstumor
中文摘要
淋巴水肿是一种无法治愈的疾病,其特征是淋巴阻塞,组织肿胀,免疫功能低下。
功能障碍和淋巴损伤后的纤维化。淋巴水肿影响着500万美国人,
由于肢体残疾、毁容和复发性威胁肢体的感染的风险而导致生活质量差。在
在美国,水肿是治疗恶性肿瘤的淋巴结清扫术最常见的结果
如乳房或盆腔肿瘤。一旦确定,这种疾病是渐进的,很难治疗。
先前证明在淋巴损伤时给予9-顺式视黄酸(9-cisRA)可以
刺激淋巴管生成和减轻小鼠疾病进展。将这些发现转化为
临床环境涉及在第二个非啮齿动物大型动物模型中证明功效。为了解决这一问题,
我们选择猪是因为它的软组织解剖学和生理学与人类更相似
比啮齿动物模型更好。虽然该提案的中心目标是确定9-顺式RA是否可以预防
本提案的两个具体目标包括目标1:确定
9-顺式RA对猪严重淋巴损伤后肢体体积、MRI特征和淋巴转运的影响;以及
目的2:观察9-顺式维甲酸(9-cis RA)对大鼠脑缺血再灌注损伤后组织病理学和分子生物学变化的影响。
猪的严重淋巴损伤。完成这一建议将产生高度相关和可翻译的调查结果
这将有助于开发基于9-顺式RA的治疗方法,以预防和管理
继发性水肿。
英文摘要
Lymphedema is an incurable condition characterized by lymphatic obstruction, tissue swelling, immune
dysfunction, and fibrosis after lymphatic injury. Lymphedema affects 5 million Americans and is associated with
poor quality of life due to extremity disability, disfigurement, and risk for recurrent limb-threatening infection. In
the US, lymphedema is most commonly a consequence of lymph node dissection for the treatment of malignancies
such as breast or pelvic tumors. Once established, this disease is progressive and difficult to treat. We have
previously demonstrated that administration of 9-cis retinoic acid (9-cis RA) at the time of lymphatic injury can
stimulate lymphangiogenesis and mitigate disease progression in mice. A critical step in translating these findings
to the clinical setting involves demonstrating efficacy in a second, non-rodent, large animal model. To address this,
we have chosen swine due to the fact that it has soft tissue anatomy and physiology that is more similar to human
than rodent models. While the central goal of this proposal will be to determine if 9-cis RA can prevent
postsurgical lymphedema in swine, the two specific aims of this proposal include Aim 1: To determine the effect of
9-cis RA on limb volume, MRI characteristics, and lymphatic transport after critical lymphatic injury in swine; and
Aim 2: To assess the effect of 9-cis RA on the histopathological and molecular changes in tissues at the site of
critical lymphatic injury in swine. Completion of this proposal will yield highly relevant and translatable findings
that will facilitate development of a 9-cis RA based therapeutic approach to prevention and management of
secondary lymphedema in humans.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.3390/bioengineering9040162
发表时间:
2022-04-06
期刊:
Bioengineering (Basel, Switzerland)
影响因子:
--
作者:
[]
通讯作者:
Retinoic Acid Induced Lymphangiogenesis for Post-surgical Lymphedema
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批准号:10186087
-
项目类别:
-
资助金额:$63.13万
-
财政年份:2021
-
负责人:Alex K. Wong
-
依托单位:
Retinoic Acid Induced Lymphangiogenesis for Post-surgical Lymphedema
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批准号:10472024
-
项目类别:
-
资助金额:$62.67万
-
财政年份:2021
-
负责人:Alex K. Wong
-
依托单位:
Retinoic Acid Induced Lymphangiogenesis for Post-surgical Lymphedema
-
批准号:10685300
-
项目类别:
-
资助金额:$70.33万
-
财政年份:2021
-
负责人:Alex K. Wong
-
依托单位:
Mitigation of lymphatic injury by retinoic acid therapy in a large animal model
-
批准号:10064586
-
项目类别:
-
资助金额:$8.25万
-
财政年份:2020
-
负责人:Alex K. Wong
-
依托单位:
Investigation of 9-cis Retinoic Acid as a Novel Treatment for Post-Surgical Lymphedema
-
批准号:9243806
-
项目类别:
-
资助金额:$17.8万
-
财政年份:2017
-
负责人:Alex K. Wong
-
依托单位:
Investigation of 9-cis Retinoic Acid as a Novel Treatment for Post-Surgical Lymphedema
-
批准号:10438477
-
项目类别:
-
资助金额:$2.57万
-
财政年份:2017
-
负责人:Alex K. Wong
-
依托单位:
Investigation of 9-cis Retinoic Acid as a Novel Treatment for Post-Surgical Lymphedema
-
批准号:9414934
-
项目类别:
-
资助金额:$17.8万
-
财政年份:2017
-
负责人:Alex K. Wong
-
依托单位:
海外基金