Cancer-related lymphedema
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Abstract:
Lymphedema is an inflammatory condition caused by the accumulation of lymphatic fluid due to damage to the lymphatic system. There are 2 classifications of lymphedema: primary, which is caused by malformation of lymph vessels or nodes, and secondary, which is due to trauma, chronic lymphatic systemKeywords:
Secondary lymphedema
Lymphangiogenesis
Most cancerous lesions metastasize through the lymphatic system and the status of regional lymph nodes is the most important indicator of a patient's prognosis. The extent of lymph node involvement with cancer is also an important parameter used for determining treatment options. Although the importance of the lymphatic system for metastasis has been well recognized, traditionally, the lymphatic vessels have not been considered actively involved in the metastatic process. Recent evidence, however, indicates that the activation of the lymphatic system is an important factor in tumor progression to metastasis. Tumor lymphangiogenesis has been associated with increased propensity for metastasis, and lymphatic vessel density has emerged as another promising prognostic indicator. More recently, lymphangiogenesis in the sentinel lymph nodes has been shown to contribute to malignant progression. In addition to its role as a transport system for tumor cells, the lymphatic system may also be more actively involved in metastases by directly facilitating tumor cell recruitment into the lymphatic vessels. This review highlights recent advances in our understanding of the mechanisms by which lymphatic vessels participate in metastasis.
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In human solid cancer, the lymph node status is the most important prognostic indicator for the clinical outcome of patients. Follow-up data has shown that about 80% of metastasis follows an orderly pattern of progression via the lymphatic network while about 20% systemic metastasis occurs, bypassing the lymphatic system. Over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumour-induced lymphangiogenesis, and the majority of studies point out to a positive correlation between tumour-induced lymphangiogenesis and lymphatic metastasis. However, the impact of intra- and peritumoural lymphatics on the tumour biology and the first steps of lymphatic metastasis, i.e. the invasion of tumour cells into the lymphatic vessels, are not well understood. We will give an outline of i. the physiological process of lymphangiogenesis, ii. tumour-induced lymphangiogenesis and lymphatic metastasis, iii. lymphatic invasion and the common pathways of tumour-lymphangiogenesis and lymphatic invasion. The growing interest in this topic has brought up a number of new molecular players in the field, which may provide the basis for a rational therapy against the process of lymphatic dissemination of tumour cells.
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Lymphatic metastasis is an important route of tumor metastasis.The structural features of lymphatic system are anatomical basis for lymphatic metastasis.The markers of lymphatic vessel can facilitate the identifiction of lymphangiogenesis.Lymphangiogenesis has been found in the intratumorous and peritumorous tissues of many malignancies.The density of neogenetic lymphatics and the expression levels of molecular markers of lymph duct are closely related to lymphatic metastasis.The study of VEGF(vascular endothelial growth factor)family provides a new approach to reveal the the mechanism of lymphatic metastasis.This article reviews the studies on tumor lymphangiogenesis and the mechanism of lymphatic metastasis.
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Lymphatic vessel
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Lymphangiogenesis
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Lymphangiogenesis
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Lymphedema is an inflammatory condition caused by the accumulation of lymphatic fluid due to damage to the lymphatic system. There are 2 classifications of lymphedema: primary, which is caused by malformation of lymph vessels or nodes, and secondary, which is due to trauma, chronic lymphatic system
Secondary lymphedema
Lymphangiogenesis
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Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor.
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Secondary lymphedema
Etiology
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Lymphatic vessels are important for the maintenance of normal tissue fluid balance, for immune surveillance and adsorption of digested fats. In spite of their important functions in physiological as well as in various pathological conditions, including tumour metastasis, lymphoedema and inflammation, the lymphatic vessels have not received as much attention as the blood vessels, and the mechanisms regulating their development and growth have been poorly understood. However, recent studies using mouse genetic tools and primary lymphatic endothelial cell cultures have greatly increased our understanding of how the lymphatic endothelial cells differentiate, how lymphatic vessel growth is regulated and how the remodelling of the lymphatic vasculature into a functional vessel network consisting of capillaries and collecting vessels occurs. Furthermore, these studies have also provided mechanistic insights into the processes involved in pathological lymphangiogenesis.
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A bstract : Metastasis of most cancers occurs primarily through the lymphatic system, and the extent of lymph node involvement is the most important prognostic indicator. While the importance of the lymphatic system as a pathway for metastasis has been well recognized, there is very little information available about the mechanisms by which tumor cells interact with the lymphatics. Recently, production of the lymphangiogenic factor VEGF‐C has been detected in tumors, and the significance of VEGF‐C‐mediated lymphangiogenesis for tumor metastasis has been demonstrated. Increased lymphatic vessel density has been found associated with certain tumors. The mechanisms by which tumor cells gain access to and enter lymphatic vessels are critical issues that need to be addressed in the future. In contrast to the prevailing view that has assigned to the lymphatic system a passive role in the metastatic process, our results indicate the importance of lymphatic vessel activation in tumor dissemination.
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The lymphatic system is important in tissue fluid balance regulation, immune cell trafficking, edema, and cancer metastasis, yet very little is known about the sequence of events that initiate and coordinate lymphangiogenesis. Here, we characterize the process of lymphatic regeneration by uniquely correlating interstitial fluid flow and lymphatic endothelial cell migration with lymphatic function. A new model of skin regeneration using a collagen implant in a mouse tail has been developed, and it shows that (1) interstitial fluid channels form before lymphatic endothelial cell organization and (2) lymphatic cell migration, vascular endothelial growth factor-C expression, and lymphatic capillary network organization are initiated primarily in the direction of lymph flow. These data suggest that interstitial fluid channeling precedes and may even direct lymphangiogenesis (in contrast to blood angiogenesis, in which fluid flow proceeds only after the vessel develops); thus, a novel and robust model is introduced for correlating molecular events with functionality in lymphangiogenesis.
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