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Nature Sep 2020Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood; however, the...
Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.
Topics: Animals; Cell Survival; Coenzyme A Ligases; Female; Ferroptosis; Glutathione; Humans; Iron; Lymph; Male; Melanoma; Mice; Neoplasm Metastasis; Oleic Acid; Oxidative Stress; Phospholipid Hydroperoxide Glutathione Peroxidase; Principal Component Analysis
PubMed: 32814895
DOI: 10.1038/s41586-020-2623-z -
Arteriosclerosis, Thrombosis, and... Jan 2021Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells.... (Review)
Review
Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.
Topics: Animals; Blood Platelets; Bone Marrow; Cell Communication; Cell-Derived Microparticles; Hemostasis; Humans; Inflammation Mediators; Lymph; Platelet Activation; Synovial Fluid
PubMed: 33028092
DOI: 10.1161/ATVBAHA.120.314644 -
Science Immunology Dec 2021Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin...
Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP). Saponin-containing adjuvants exhibited distinctive mechanisms of action, altering lymph flow in a mast cell–dependent manner and promoting antigen entry into draining lymph nodes. SMNP was particularly effective, exhibiting even greater potency than the compositionally related adjuvant AS01 in mice, and primed robust germinal center B cell, T, and HIV tier 2 neutralizing antibodies in nonhuman primates. Together, these findings shed new light on mechanisms by which saponin adjuvants act to promote the immune response and suggest that SMNP may be a promising adjuvant in the setting of HIV, SARS-CoV-2, and other pathogens.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Animals; B-Lymphocytes; CD4-Positive T-Lymphocytes; Female; Lymph; Macaca mulatta; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanoparticles; Rats; Rats, Wistar; Saponins; Toll-Like Receptors
PubMed: 34860581
DOI: 10.1126/sciimmunol.abf1152 -
Immunity Dec 2021Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their...
Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNF mice, a model of ileitis, revealed TLO formation at valves of CLVs. TLOs obstructed cellular and molecular outflow from the gut and were sites of lymph leakage and backflow. Tumor necrosis factor (TNF) neutralization begun at early stages of TLO formation restored lymph transport. However, robustly developed, chronic TLOs resisted regression and restoration of flow after TNF neutralization. TNF stimulation of cultured lymphatic endothelial cells reprogrammed responses to oscillatory shear stress, preventing the induction of valve-associated genes. Disrupted transport of immune cells, driven by loss of valve integrity and TLO formation, may contribute to the pathology of Crohn's disease.
Topics: Animals; Cell Movement; Cells, Cultured; Crohn Disease; Disease Models, Animal; Endothelial Cells; Humans; Ileitis; Ileum; Lymph; Lymphangitis; Lymphatic Vessels; Mesentery; Mice; Mice, Knockout; Stress, Mechanical; Tertiary Lymphoid Structures; Tumor Necrosis Factor-alpha
PubMed: 34788601
DOI: 10.1016/j.immuni.2021.10.003 -
Lymphology 2020[Editorial] Lymphatic vessels and lymph are a missing link in SARS-CoV-2/COVID-19 pathophysiology and therapeutic strategies. Based on well-established principles of...
[Editorial] Lymphatic vessels and lymph are a missing link in SARS-CoV-2/COVID-19 pathophysiology and therapeutic strategies. Based on well-established principles of lymphatic function and dysfunction and a neglected literature, this article highlights promising directions for future research and clinical exploration.
Topics: COVID-19; Drainage; Humans; Lymph; Lymphatic Vessels; SARS-CoV-2
PubMed: 33350283
DOI: No ID Found -
ACS Biomaterials Science & Engineering Jun 2022Lymph node mapping for tumor micrometastasis is of great significance for the prevention, prognosis, and treatment of cancer. Currently, the traditional clinical... (Review)
Review
Lymph node mapping for tumor micrometastasis is of great significance for the prevention, prognosis, and treatment of cancer. Currently, the traditional clinical detection methods (computed tomography, magnetic resonance imaging, or positron emission tomography/computed tomography) in clinical lymph node mapping still have some inherent disadvantages, which have prompted the development of various fluorescent probes for lymph node mapping. However, the conventional fluorescent probes such as indocyanine green or methylene blue in lymph node mapping are still accompanied by several problems such as impaired surgical field vision due to dye staining or less accumulation and shorter retention time in the lymph node. In a recent achievement, newly designed nanoparticles are prepared with novel properties that could be attractive for lymph node mapping. In this review, we will provide details on the progress of various nanoparticles for lymph node mapping and emphasize other multivariant properties in different nanoparticles, including strong tumor-targeting affinity and specificity, self-luminescence, and even with the function to kill metastatic cancer cells.
Topics: Fluorescent Dyes; Humans; Lymph Nodes; Lymphatic Metastasis; Neoplasm Micrometastasis; Sentinel Lymph Node Biopsy
PubMed: 35548973
DOI: 10.1021/acsbiomaterials.2c00111 -
Physiological Reports May 2022The lymphatic system is compromised in different groups of patients. To recognize pathology, we must know what is healthy. We use Near-Infrared Fluorescence (NIRF) to...
The lymphatic system is compromised in different groups of patients. To recognize pathology, we must know what is healthy. We use Near-Infrared Fluorescence (NIRF) to assess peripheral lymphatic function in humans. We have shown that external factors such as exercise, hyperthermia, and pharmacological mediators influence the function of peripheral lymphatic vessels. In this study, we explored the impact on lymphatic vessels by the ever-present external factor-gravity. We used NIRF imaging to investigate the lymphatic changes to gravity. Gravity was assessed by changing body position from supine to standing. We extracted following lymphatic functional parameters: lymphatic packet propulsion frequency (contractions/min), velocity (cm/s), and pressure (mmHg). Raw data analysis was performed using a custom-written Labview program. All sequences were analyzed by two observers and interclass correlation scores were calculated. All statistical analysis was performed using RStudio Team (2021). RStudio: Integrated Development Environment for R. RStudio, PBC. Healthy participants (n = 17, 11 males, age 28.1 ± 2.6 years) were included. The lymphatic packet propulsion frequency at baseline was 0.5 ± 0.2 contractions/min and rose within 3 min significantly to a maximum of 1.2 ± 0.5 contractions/min during upright posture and remained significantly higher than the baseline lymphatic packet propulsion frequency after lying down again for up to 6 min. The lymph velocity was 1.5 ± 0.4 cm/s at baseline and changed in both directions and without a specific pattern at different points in time during standing. Lymph pressure was significantly higher while standing (mean increase 9 mmHg, CI: 2-15 mmHg). The ICC scores were 89.8% (85.9%-92.7%), 59.3% (46.6%-69.6%) and 89.4% (79.0%-94.8%) in lymphatic packet propulsion frequency (130 observations), velocity (125 observations), and pressure (30 observations), respectively. The lymphatic system responds within few minutes to gravitational changes by increasing lymphatic packet propulsion frequency and pressure.
Topics: Adult; Gravitation; Humans; Lymph; Lymphatic Vessels; Male; Optical Imaging; Posture
PubMed: 35586957
DOI: 10.14814/phy2.15289 -
Journal of Surgical Oncology Feb 2023Lung cancer is a deadly disease. Lymph node staging is the most important prognostic factor, and lymphatic drainage of the lung is complex. Major advances have been made... (Review)
Review
Lung cancer is a deadly disease. Lymph node staging is the most important prognostic factor, and lymphatic drainage of the lung is complex. Major advances have been made in this field over the last several decades, but there is much left to understand and improve upon. Herein, we review the history of the lymphatic system and the creation of lymph node maps, the evolution of tumor, node, and metastasis lung cancer classification, the importance of lung cancer staging, techniques for lymph node dissection, and our recommendations regarding a minimum number of nodes to sample during pulmonary resection.
Topics: Humans; Lymphatic Metastasis; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lung; Neoplasm Staging; Prognosis
PubMed: 36630092
DOI: 10.1002/jso.27157 -
Rozhledy V Chirurgii : Mesicnik... 2020The spectrum of causes of chylothorax is wide, including an injury to the thoracic duct in various thoracosurgical procedures, especially in esopha-geal, lung and heart...
The spectrum of causes of chylothorax is wide, including an injury to the thoracic duct in various thoracosurgical procedures, especially in esopha-geal, lung and heart surgery. Late diagnosis or inadequate treatment of chylothorax still has a high rate of morbidity and mortality. This is mainly related to high losses of chyle which is rich in minerals, plasma proteins, fats and lymphocytes. The most serious effects are mineral breakdown, malnutrition and immunodeficiency. Early diagnosis and adequate therapy are essential. The strategy is based on the type of primary operation, the volume of chyle secretion and its duration. The authors present an overview of the issue of chylothorax from its etiology of origin to its anatomy, physiology, pathophysiology, symptomatology, diagnosis and therapy.
Topics: Chyle; Chylothorax; Humans; Ligation; Thoracic Duct
PubMed: 33242960
DOI: No ID Found