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Molecular Diagnosis & Therapy 2007Substantial advances have accrued over the last decade in the identification of the processes that contribute to lymphatic vascular development in health and disease.... (Review)
Review
Substantial advances have accrued over the last decade in the identification of the processes that contribute to lymphatic vascular development in health and disease. Identification of distinct regulatory milestones, from a variety of genetic models, has led to a stepwise chronology of lymphatic development. Several molecular species have been identified as important tissue biomarkers of lymphatic development and function. At present, vascular endothelial growth-factor receptor (VEGFR)-3/VEGF-C/VEGF-D signaling has proven useful in the identification of clinical lymphatic metastatic potential and the assessment of cancer prognosis. Similar biomarkers, to be utilized as surrogates for the assessment of inherited and acquired diseases of the lymphatic circulation, are actively sought, and will represent a signal advance in biomedical investigation.
Topics: Animals; Biomarkers; Humans; Lymphangiogenesis; Lymphatic Diseases; Lymphatic System; Lymphedema
PubMed: 17705577
DOI: 10.1007/BF03256244 -
Annals of the New York Academy of... 2008Genetic studies of inherited lymphedema have provided the starting point for the molecular dissection of lymphatic development and disease. Here, we update the recent... (Review)
Review
Genetic studies of inherited lymphedema have provided the starting point for the molecular dissection of lymphatic development and disease. Here, we update the recent contribution of the study of inherited lymphedema and discuss the parallels between mouse models of lymphedema and inherited lymphedema. That the known mutations leading to lymphatic phenotypes explain fewer than half the cases of lymphedema means that the continued study of these disorders may reveal new pathways in lymphatic biology.
Topics: Animals; Forkhead Transcription Factors; Humans; Lymphangiogenesis; Lymphatic Diseases; Lymphedema; Noonan Syndrome; Research
PubMed: 18519966
DOI: 10.1196/annals.1413.012 -
Vascular Medicine (London, England) Jun 2010Despite the central, complex role for the lymphatic system in the maintenance of human health, the biology of this important and complex vasculature has been relatively... (Review)
Review
Despite the central, complex role for the lymphatic system in the maintenance of human health, the biology of this important and complex vasculature has been relatively under-investigated. However, the last decade has witnessed a substantial growth in the elucidation of lymphatic structural biology and the function of this system in health and in disease. These newly gained insights can be used to formulate our evolving concepts about the diagnostic and therapeutic approaches to patients with lymphatic vascular disorders. In lymphedema, there is a spectrum of disease that extends from primary (heritable) to secondary (acquired) causes. Once detected, the presence of lymphatic edema mandates very specific modalities of intervention, predominated by physiotherapeutic techniques. In addition, a physiological basis for adjunctive, intermittent pneumatic compression has been established, and these modalities may be indicated in selected patient populations. The acknowledgement of a unique biology in lymphatic edemas is, increasingly, guiding research efforts within this field. Increasing investigative attention is being directed toward animal models of lymphatic vascular disease. As insight into the complex biology of the lymphatic vasculature continues to expand through focused biomedical investigation, the translation of these mechanistic insights into targeted, rationally conceived therapeutics will become increasingly feasible.
Topics: Humans; Lymphatic Diseases; Risk Factors; Vascular Diseases
PubMed: 20483987
DOI: 10.1177/1358863X10364553 -
Genes & Development Oct 2010The lymphatic vascular system is essential for lipid absorption, fluid homeostasis, and immune surveillance. Until recently, lymphatic vessel dysfunction had been... (Review)
Review
The lymphatic vascular system is essential for lipid absorption, fluid homeostasis, and immune surveillance. Until recently, lymphatic vessel dysfunction had been associated with symptomatic pathologic conditions such as lymphedema. Work in the last few years had led to a better understanding of the functional roles of this vascular system in health and disease. Furthermore, recent work has also unraveled additional functional roles of the lymphatic vasculature in fat metabolism, obesity, inflammation, and the regulation of salt storage in hypertension. In this review, we summarize the functional roles of the lymphatic vasculature in health and disease.
Topics: Animals; Humans; Lymphatic Diseases; Lymphatic Vessels
PubMed: 20889712
DOI: 10.1101/gad.1955910 -
Lymphatic Research and Biology 2008The convergence of multiple disciplines upon the study of the lymphatic vasculature has invigorated a renaissance of research, using powerful investigative tools and an... (Review)
Review
The convergence of multiple disciplines upon the study of the lymphatic vasculature has invigorated a renaissance of research, using powerful investigative tools and an exponential growth of interest in this historically underappreciated system. Fundamental discoveries in lymphatic development have yielded relevant animal models for vexing clinical diseases that suffer from nonexistent of minimally effective treatments. Inherited and acquired lymphedema represent the current crux of research efforts to identify potential molecular therapies born from these early discoveries. The importance of the lymphatic system is, however, not limited to lymphedema but encompasses a diverse spectrum of human disease including inflammation and cancer metastasis. As the lymphatic vasculature continues to benefit from fruits of biomedical investigation, translation of mechanistic insights into targeted, rationally-conceived therapeutics will be become a reality.
Topics: Allergy and Immunology; Animals; Drug Design; Gene Expression Regulation; Humans; Inflammation; Lymphangiogenesis; Lymphatic Diseases; Lymphatic System; Lymphatic Vessels; Lymphedema; Models, Biological; Neoplasm Metastasis; Treatment Outcome
PubMed: 19093791
DOI: 10.1089/lrb.2008.63404 -
Current Problems in Cancer Dec 2019Axillary web syndrome (AWS) refers to the development of fibrotic bands or "cords" in the axilla of patients who have undergone axillary lymph node dissection for breast... (Review)
Review
Axillary web syndrome (AWS) refers to the development of fibrotic bands or "cords" in the axilla of patients who have undergone axillary lymph node dissection for breast cancer. We review the incidence, pathogenesis, risk factors, and management of AWS. AWS is a common complication in patients who undergo axillary lymph node dissection. Even though AWS is self-limited in most cases, it causes significant morbidity. The optimal management of AWS is unclear but physiotherapy appears to be beneficial. The widespread use of less invasive procedures to evaluate the presence of metastasis in the axillary lymph nodes (ie, sentinel lymph node biopsy) is expected to reduce the incidence of AWS. The close collaboration of surgeons, oncologists, and physiotherapists is necessary for the prevention and management of this frequent condition.
Topics: Axilla; Breast Neoplasms; Disease Management; Female; Humans; Incidence; Lymph Node Excision; Lymphatic Diseases; Syndrome
PubMed: 30898366
DOI: 10.1016/j.currproblcancer.2019.02.002 -
Radiographics : a Review Publication of... 2022Lymphatic abnormalities encompass a wide range of disorders spanning solitary common cystic lymphatic malformations (LMs) to entities involving multiple organ systems... (Review)
Review
Lymphatic abnormalities encompass a wide range of disorders spanning solitary common cystic lymphatic malformations (LMs) to entities involving multiple organ systems such as lymphangioleiomyomatosis. Many of these disorders are rare, yet some, such as secondary lymphedema from the treatment of malignancy (radiation therapy and/or lymph node dissection), affect millions of patients worldwide. Owing to complex and variable anatomy, the lymphatics are not as well understood as other organ systems. Further complicating this is the variability in the description of lymphatic disease processes and their nomenclature in the medical literature. In recent years, medical imaging has begun to facilitate a deeper understanding of the physiology and pathologic processes that involve the lymphatic system. Radiology is playing an important and growing role in the diagnosis and treatment of many lymphatic conditions. The authors describe both normal and common variant lymphatic anatomy. Various imaging modalities including nuclear medicine lymphoscintigraphy, conventional lymphangiography, and MR lymphangiography used in the diagnosis and treatment of lymphatic disorders are highlighted. The authors discuss imaging many of the common and uncommon lymphatic disorders, including primary LMs described by the International Society for the Study of Vascular Anomalies 2018 classification system (microcystic, mixed, and macrocystic LMs; primary lymphedema). Secondary central lymphatic disorders are also detailed, including secondary lymphedema and chylous leaks, as well as lymphatic disorders not otherwise easily classified. The authors aim to provide the reader with an overview of the anatomy, pathology, imaging findings, and treatment of a wide variety of lymphatic conditions. RSNA, 2022.
Topics: Humans; Lymphatic Diseases; Lymphatic System; Lymphedema; Lymphography; Magnetic Resonance Imaging
PubMed: 35179984
DOI: 10.1148/rg.210104 -
Annals of the New York Academy of... Dec 2002The human disease states that are characterized by functional lymphatic insufficiency currently lack a cure. Molecular approaches may ultimately provide a therapeutic... (Review)
Review
The human disease states that are characterized by functional lymphatic insufficiency currently lack a cure. Molecular approaches may ultimately provide a therapeutic window to reverse the stigmata of both primary and secondary lymphatic insufficiency. To harness the potential therapeutic power of lymphangiogenesis, testing the safety and efficacy of the treatment response will be necessary. This, in turn, necessitates the availability of suitable preclinical animal models of the disease processes in question, along with suitable research tools to permit an assessment of the response to applied therapies. An ideal model would reproducibly and inexpensively replicate the untreated disease of human lymphedema. It would closely simulate the biology, as we understand it, of the human disease, and would replicate both the pathogenesis of the disease, including its natural history and the temporal patterns of its clinical expression. In this way, one might aspire to make valid predictions about the human applicability of therapy by extrapolation from observations in animal models. In addition to the availability of suitable animal models, the required investigative tools must also be available. In the context of lymphangiogenesis, to assess the therapeutic response, one must certainly possess the ability to recognize newly developed lymphatic vasculature. Sophisticated immunohistochemical and imaging techniques make this increasingly feasible. Initial experimental observations indicate that growth factor and gene therapy with VEGF-C holds promise for the treatment of both primary and secondary forms of lymphedema.
Topics: Animals; Disease Models, Animal; Genetic Therapy; Growth Substances; Humans; Lymph; Lymphatic Diseases; Rats
PubMed: 12543717
DOI: 10.1111/j.1749-6632.2002.tb04868.x -
Current Opinion in Pediatrics Jun 2018The essential role of the lymphatic system in fluid homeostasis, nutrient transport, and immune trafficking is well recognized; however, there is limited understanding... (Review)
Review
PURPOSE OF REVIEW
The essential role of the lymphatic system in fluid homeostasis, nutrient transport, and immune trafficking is well recognized; however, there is limited understanding of the mechanisms that regulate lymphatic function, particularly in the setting of critical illness. The lymphatics likely affect disease severity and progression in every condition, from severe systemic inflammatory states to respiratory failure. Here, we review structural and functional disorders of the lymphatic system, both congenital and acquired, as they relate to care of the pediatric patient in the intensive care setting, including novel areas of research into medical and procedural therapeutic interventions.
RECENT FINDINGS
The mainstay of current therapies for congenital and acquired lymphatic abnormalities has involved nonspecific medical management or surgical procedures to obstruct or divert lymphatic flow. With the development of dynamic contrast-enhanced magnetic resonance lymphangiography, image-directed percutaneous intervention may largely replace surgery. Because of new insights into the mechanisms that regulate lymphatic biology, pharmacologic inhibitors of mTOR and leukotriene B4 signaling are each in Phase II clinical trials to treat abnormal lymphatic structure and function, respectively.
SUMMARY
As our understanding of normal lymphatic biology continues to advance, we will be able to develop novel strategies to support and augment lymphatic function during critical illness and through convalescence.
Topics: Child; Critical Care; Critical Illness; Heart Diseases; Humans; Lymphatic Diseases; Multiple Organ Failure
PubMed: 29538048
DOI: 10.1097/MOP.0000000000000623 -
Journal of Biophotonics Aug 2018In vivo visualization of the human lymphatic system is limited by the mode of delivery of tracing agents, depth of field and size of the area examined, and specificity... (Review)
Review
In vivo visualization of the human lymphatic system is limited by the mode of delivery of tracing agents, depth of field and size of the area examined, and specificity of the cell markers used to distinguish lymphatic endothelium from the blood vessels and the surrounding tissues. These limitations are particularly problematic when imaging human lymphatic abnormalities. First, limited understanding of the lymphatic disease aetiology exists with respect to genetic causes and phenotypic presentations. Second, the ability of a tracer to reach the entire lymphatic network within the diseased tissue is suboptimal. Third, what is known about the expression of lymphatic endothelial cell (LEC) markers, such as podoplanin, lymphatic vessel endothelial hyaluronan receptor, Drosophila melanogaster homeobox gene prospero-1 and vascular endothelial growth factor receptor-3 in rodent lymphatic vessels and healthy human LECs may not necessarily apply in human lymphatic disease settings. The aim of this review is to highlight challenges in visualizing lymphatic vessels in human lymphatic abnormalities with respect to distribution patterns of the cellular markers currently employed to visualize abnormal human lymphatic vessels in experimental settings. Allowing for these limitations within new diagnostic visualization technologies is likely to improve our ability to image human lymphatic diseases.
Topics: Animals; Biomarkers; Humans; Lymphatic Abnormalities; Lymphatic System
PubMed: 28869350
DOI: 10.1002/jbio.201700117