The mechanisms by which vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) contribute to lung cancer growth have not been fully elucidated. This study aimed to assess the role of VEGF and sICAM-1 in control of pleural effusions (PE) and survival in patients with primary human lung ...

OBJECTIVE: To examine the potential for treatment of palmar adhesions associated with Dupuytren's contracture using instrument-assisted cross-frictional massage (CFM) and stretching. METHODS: This was a prospective case study. The primary intervention consisted of a 2-min multi-planar CFM over the affected area of the palm, followed by a 2-min maximal finger-extension ...

Pemphigus is a group of autoimmune blistering diseases characterized by blisters and erosive lesions on the skin and mucous membranes due to loss of cell and cell adhesion of keratinocytes. In 2010, new Japanese guidelines for the management of pemphigus were published for dermatologists. Systemic corticosteroids are the gold standard ...

Over the past decade, many changes and updates have occurred in the world of vascular anomalies, including their histopathology. An appreciation has developed that a combined team approach is optimal in arriving at a correct diagnosis. Technical advances such as immunohistochemical stains for GLUT1, an excellent marker for infantile hemangioma, ...

An asymptomatic, bluish-gray, movable, raised, and firm left upper eyelid mass had been present for 8 months in an 82-year-old woman. Histopathologic examination revealed a lesion restricted to the dermis and composed in part of a calcific nodule that was circumscribed by an acellular fibrous capsule. An adjacent nodule exhibited ...

Endostatin has potent anti-endothelial and anti-angiogenic functions. Endostatin was reported to reduce lymphangiogenesis by down-regulating the level of VEGF-C in tumour tissues. However, there is little evidence for the direct function of endostatin on lymphangiogenic endothelial cells and lymphangiogenic vessels. Here, we report that cell surface nucleolin, which was reported ...

Macrophages have been suggested to stimulate neo-lymphangiogenesis in settings of inflammation via two potential mechanisms: (1) acting as a source of lymphatic endothelial progenitor cells via the ability to transdifferentiate into lymphatic endothelial cells and be incorporated into growing lymphatic vessels; and (2) providing a crucial source of pro-lymphangiogenic growth ...

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate ...

The homeobox transcription factor PROX1 is essential for the development and maintenance of lymphatic vasculature. How PROX1 regulates lymphatic endothelial cell fate remains undefined. PROX1 has been shown to upregulate the expression of Cyclin E, which mediates the G(1) to S transition of the cell cycle. Here we demonstrate that ...

Axillary dissection during breast cancer surgery produces extensive lymphatic vessel damage that often leads to lifelong secondary lymphedema of the arm. We have developed a biodegradable material conduit for lymphatic vessel reconstruction where fibers electrospun along the conduit lumen promote endothelial cell alignment and migration in vitro. The diameter and ...

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs ...

The pulmonary lymphatic vasculature plays a vital role in maintaining fluid homeostasis required for efficient gas exchange at capillary alveolar barriers and contributes to lung fluid clearance at birth. To further understanding of pulmonary lymphatic function at birth, lineage-tracing analysis of mouse lung was used. Lineage analysis confirmed that lymphatic ...

Fibrillin microfibrils constitute a scaffold for elastin deposition in the wall of arteries and form the anchoring filaments that connect the lymphatic endothelium to surrounding elastic fibers. We previously reported that fibrillin is deposited in a honeycomb pattern in bovine arterial endothelial cells, which also deposit microfibril-associated glycoprotein (MAGP)-1, whereas ...

The lymphatic circulation mediates drainage of fluid and cells from the periphery through lymph nodes, facilitating immune detection of lymph-borne foreign Ags. The 10.1.1 mAb recognizes a lymphatic endothelial Ag, in this study purified by Ab-affinity chromatography. SDS-PAGE and mass spectrometry identified murine chloride channel calcium-activated 1 (mCLCA1) as the ...

The vascular endothelial growth factor (VEGF) family of secreted proteins and their receptors are major regulators of blood vessel development (hemangiogenesis) and lymphatic vessel development (lymphangiogenesis). VEGF acts through a complex system of receptor tyrosine kinases, which can be membrane bound or soluble. New data concerning the receptor system are ...

Small leucine-rich repeat proteoglycans (decorin, biglycan, and lumican), collagen, and lymphangiogenesis are involved in tissue remodelling of various organs with inflammatory diseases. We determined the expression level and the distribution pattern of small leucine-rich repeat proteoglycans (decorin, biglycan, and lumican), collagen and lymphatic vessels in healthy, mild, and severe persistent ...

Recent findings indicate that VEGF receptors and coreceptors (neuropilins; NRP) are expressed on nonendothelial cells in human bladder urothelium, in one human bladder cancer cell line (J82), and in the mouse bladder urothelium. In addition, VEGFR1, VEGFR2, NRP1, and NRP2 expressions were upregulated in animal models of chronic bladder inflammation ...

Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood ...

Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell function has yet to be identified. Here, we investigate the identity of BM-derived lymphatic endothelial progenitor cells and their role in lymphatic neovascularization. ...

The lymphatic vasculature is essential for the recirculation of extracellular fluid, fat absorption, and immune function and as a route of tumor metastasis. The dissection of molecular mechanisms underlying lymphangiogenesis has been accelerated by the identification of tissue-specific lymphatic endothelial markers and the study of congenital lymphedema syndromes. We report ...

ABSTRACT: INTRODUCTION: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, postsurgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous ...

The lymphatic system is important for body fluid balance as well as immunological surveillance. Due to the identification of new molecular markers during the last decade, there has been a recent dramatic increase in our knowledge on the molecular mechanisms involved in lymphatic vessel growth (lymphangiogenesis) and lymphatic function. Here ...

Lysophosphatidic acid (LPA) is a potent lipid mediator with a wide variety of biological actions mediated through G protein-coupled receptors (LPA(1-6)). LPA(4) has been identified as a G(13) protein-coupled receptor, but its physiological role is unknown. Here we show that a subset of LPA(4)-deficient embryos did not survive gestation and ...

Angio- and lymphangiogenesis are inherently related processes. However, how blood and lymphatic vessels regulate each other is unknown. This work introduces a novel mechanism explaining the temporal and spatial relation of blood and lymphatic vessels. Vascular endothelial growth factor-A (VEGF-A) surprisingly reduced VEGF-C in the supernatant of blood vessel endothelial ...

The molecular mechanisms involved in lymphangiogenesis were unknown until recently. We previously demonstrated that the endothelin-1 (ET-1) axis stimulates lymphatic endothelial cells (LEC) and lymphatic vessels to grow and invade. Here we further investigated the effect of ET-1 on lymphatic vessels and evaluated whether ET-1 actions result in the functional ...

Analyses of microvascular networks with traditional tracer filling techniques suggest that the blood and lymphatic systems are distinct without direct communications, yet involvement of common growth factors during angiogenesis and lymphangiogenesis suggest that interactions at the capillary level are possible. To investigate the structural basis for lymphatic/blood endothelial cell connections ...

The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk consisting of three types of ...

Lymphangiogenesis induced during tumor growth contributes to metastasis. Genetic and chemical screens using the zebrafish model have the potential to enhance our understanding of lymphangiogenesis, and lead to the discovery of pharmacological agents with activity in the lymphatic system. Large-scale screening of lymphatic development in the whole zebrafish embryo requires ...

To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed ...

The lymphatic vascular system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined by comparative transcriptional profiling studies of ex vivo isolated mouse intestinal lymphatic endothelial cells versus blood vascular endothelial cells, thymus cell antigen 1 (Thy1, CD90) was expressed ...

The specification of arterial, venous, and lymphatic endothelial cell fate is critical during vascular development. Although the homeobox transcription factor, Prox1, is crucial for the specification and maintenance of lymphatic endothelial cell identity, little is known regarding the mechanisms that regulate Prox1 expression. Here we demonstrate that miR-181a binds the ...

The structural and molecular properties of the human tonsil lymphatic microvascular system are important to understand as these features likely contribute to fluid balance, immunity, and tumor metastasis. The tonsil is a unique lymphoid organ in that it is in intimate contact with the contents of the upper aerodigestive tract ...

BACKGROUND/AIM: This study was designed to investigate the clinical significance of lymphangiogenic vascular endothelial growth factors C and D, and chemokine receptor CCR7 in the lymphatic spread of gastric cancer. PATIENTS AND METHODS: The expressions of VEGF-C and -D, and CCR7 were examined in 82 gastric tumors showing a discrepancy ...

During the early stages of angiogenesis, following stimulation of endothelial cells by vascular endothelial growth factor (VEGF), the vascular wall is breached, allowing high molecular weight proteins to leak from the vessels to the interstitial space. This hallmark of angiogenesis results in deposition of a provisional matrix, elevation of the ...

To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development. In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch ...

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was ...

The groundbreaking discovery about arterial and venous expression of ephrinB2 and EphB4, respectively, in early embryonic development has led to a new paradigm for vascular research, providing compelling evidence that arterial and venous endothelial cells are established by genetic mechanisms before circulation begins. For arterial specification, vascular endothelial growth factor ...

Netrin-4, a laminin-related secreted protein is an axon guidance cue recently shown essential outside of the nervous system, regulating mammary and lung morphogenesis as well as blood vascular development. Here, we show that Netrin-4, at physiologic doses, induces proliferation, migration, adhesion, tube formation and survival of human lymphatic endothelial cells ...

The clinical study for lingual disease requires the detailed investigation of the lingual lymphatic network and lymphatic marker-positive cells. Recently, it has been reported that several tissue cells and leukocytes express lymphatic markers, LYVE-1 and podoplanin. This study was aimed to clarify the lingual distribution of cells expressing LYVE-1 and ...

Endothelial cells are found in most organs and tissues in our body. Despite their apparent morphological and functional similarities, endothelial cells exhibit remarkable heterogeneity and plasticity. In a strict sense, no two endothelial cells are identical in terms of their biological, immunological, functional, metabolic, morphological, and anatomical aspects. Their heterogeneity ...

The endothelium is composed of specialized epithelial cells that line the vasculature, the lymph vessels, and the heart. These endothelial cells are characterized by their stratification and are connected via intercellular junctions that confer specific permeability. Although all endothelium acts as a barrier, considerable heterogeneity exists among different organs and ...

Arteriovenous-lymphatic endothelial cell fates are specified by the master regulators, namely, Notch, COUP-TFII, and Prox1. Whereas Notch is expressed in the arteries and COUP-TFII in the veins, the lymphatics express all 3 cell fate regulators. Previous studies show that lymphatic endothelial cell (LEC) fate is highly plastic and reversible, raising ...

Lymphatic vessels are essential for tissue homeostasis and immune surveillance and contribute to pathological conditions. Lymphatic endothelium differentiates from veins and forms an independent vascular tree with only few connections to the venous circulation. Failure of blood and lymphatic vessel separation results in hemorrhage and edema. VEGF-C and -D are ...

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis, and excess VEGF-C has been shown to be ameliorative for edema produced by lymphatic obstruction in experimental models. However, it has recently been shown that edema can resolve in the mouse tail even in the complete absence of capillary lymphangiogenesis when ...

Mammalian Ras, which is encoded by three independent genes, has been thought to be a versatile component of intracellular signalling. However, when, where and how Ras signalling plays essential roles in development and whether the three Ras genes have overlapping functions in particular cells remain unclear. Here, we show that ...

Stem cell marker nestin has been reported to be activated in various neoplasms, and its expression is correlated with poor prognosis. However, nestin expression in non-small cell lung cancer still remains unclear. The present study aimed to investigate nestin expression in 52 tissue samples of non-small cell lung cancer by ...

Lymphatic transport of peripheral interstitial fluid and dendritic cells (DCs) is important for both adaptive immunity and maintenance of tolerance to self-antigens. Lymphatic drainage can change rapidly and dramatically on tissue injury or inflammation, and therefore increased fluid flow may serve as an important early cue for inflammation; however, the ...

Lineage commitment and differentiation into mature cell types are mostly considered to be unidirectional and irreversible processes. However, recent results have challenged this by showing that terminally differentiated cell types can be reprogrammed into other cell types, an important step towards devising strategies for gene therapy and tissue regeneration. In ...

AIMS: The term lymphangiosarcoma has largely been abandoned in the current classification of endothelial neoplasms. Recently, a number of lymphatic-associated antibodies have been developed for immunohistochemistry, which frequently stain angiosarcomas, implying lymphatic or mixed lymphatic and blood vascular differentiation is common. The aim was to investigate further lymphatic antigen expression, ...

The lymphatic system plays a critical role in melanoma metastasis, and yet, virtually no information exists regarding the cellular and molecular mechanisms that take place between melanoma cells and the lymphatic vasculature. Here, we generated B16-F1 melanoma cells that expressed high (B16alpha(4)+) and negligible (B16alpha(4)-) levels of alpha(4) integrin to ...