Результаты поиска

Survey of risk factors contributed to lymphatic metastasis in patients with oral tongue cancer by immunohistochemistry.

OBJECTIVES: The aim of this study was to define the biomarkers of lymphatic spread which facilitate the appropriate therapy for oral tongue squamous cell carcinoma (OTSCC) patients at early stage. Here, we investigated the expression levels of seven biomarkers in oral squamous cell carcinoma (OSCC) tissues as well as their associations with the clinicopathologic features of OTSCC patients. METHODS: The OTSCC samples were obtained from 138 patients undergoing tumor resection. Immunohistochemical staining was performed by using ColIA, ColIVA, Fn1, MMP-1, MMP-2, uPA, and D2-40 antibodies. Expres

Plump endothelial cells integrated into pre-existing venules contribute to the formation of 'mother' and 'daughter' vessels in pyogenic granuloma: possible role of galectin-1, -3 and -8.

INTRODUCTION: Pyogenic granuloma (PG) is a reactive inflammatory vascular lesion of the skin and mucous membranes, characterised by the presence of enlarged venules and seamed and seamless capillaries with plump endothelial cells (EC), and numerous macrophages. EC activation upregulates the synthesis of galectins and induces their translocation to the EC surface promoting angiogenesis and lymphangiogenesis, particularly galectin-1 (Gal-1), Gal-3 and Gal-8. However, the presence and distribution of Gal-1, -3 and -8, as well as their implications in the pathogenesis of PG, has not been considere…

E2F1 Signalling is Predictive of Chemoresistance and Lymphogenic Metastasis in Penile Cancer: A Pilot Functional Study Reveals New Prognostic Biomarkers.

BACKGROUND: For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. OBJECTIVE: To identify functional biomarkers that can predict malignant progression and treatment responsiveness. DESIGN, SETTING, AND PARTICIPANTS: We used four patient-derived PC cell lines and measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and protein expression. Data were further validated in E2F1 transcription factor knockdown and overexpression experiments. We quantified E2F1 transcript levels in a set of nonmetastatic tumours (NM), metas

Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis.

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothe

Normal cardiac lymphatics and their mimics.

Significant lymphatic structural remodeling and dysfunction have been observed in preclinical models of cardiovascular disease. However, a detailed understanding of the normal structure and distribution of lymphatic vessels (LyVs) in the heart is still lacking. The goal of this study is to define the pattern of LyVs at various cardiac anatomical sites using Prox1-tdTomato lymphatic reporter mice. By light sheet microscopy, we first confirmed the presence of an extensive network of LyVs on the epicardial surface of the ventricles, while minimal signal was detected on the atria. We then evaluate

Blockade of prolymphangiogenic vascular endothelial growth factor C in dry eye disease.

OBJECTIVE: To determine whether blocking prolymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) would suppress alloimmunity in dry eye disease using a murine model. METHODS: The effects of intraperitoneal injections of 400 μg of anti-VEGF-C antibody (treated group) and intraperitoneal normal saline (untreated group) were studied in murine dry eyes induced by exposing mice to high-flow desiccated air in a controlled-environment chamber. Growth of lymphatic vessels and infiltration of macrophages were evaluated by immunohistochemistry using CD31 (panendothelial marker)

Broad targeting of angiogenesis for cancer prevention and therapy.

Deregulation of angiogenesis--the growth of new blood vessels from an existing vasculature--is a main driving force in many severe human dis … cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the av …

VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours.

Immune surveillance against pathogens and tumours in the central nervous system is thought to be limited owing to the lack of lymphatic drainage. However, the characterization of the meningeal lymphatic network has shed light on previously unappreciated ways that an immune response can be elicited to antigens that are expressed in the brain1-3. Despite progress in our understanding of the development and structure of the meningeal lymphatic system, the contribution of this network in evoking a protective antigen-specific immune response in the brain remains unclear. Here, using a mouse model o

The YAP signaling pathway promotes the progression of lymphatic malformations through the activation of lymphatic endothelial cells.

BACKGROUND: To investigate whether the YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ binding motif) pathway contributes to the pathogenesis of lymphatic malformations (LMs). METHODS: YAP, TAZ, CTGF (connective tissue growth factor), and Ki-67 were detected in LMs by immunohistochemistry. The colocalization of YAP and Ki-67 was analyzed by double immunofluorescence. Pearson's correlation and cluster analyses were performed to analyze the relationships between these proteins. Human dermal lymphatic endothelial cells (HDLECs) were used for mechanistic investigation. Rat mo

Clinical significance of FAP-α on microvessel and lymphatic vessel density in lung squamous cell carcinoma.

AIMS: We aimed to determine whether cancer-associated fibroblasts (CAFs) are associated with microvessel density (MVD) and lymphatic vessel density (LVD) in lung squamous cell carcinoma, as well as their clinical significance in predicting survival. METHODS: 122 patients were enrolled in the study. Samples were obtained on resection at the Department of Thoracic Surgery of the Qingdao Municipal Hospital between January 2011 and December 2014. Immunohistochemistry was used to determine vessel and lymphatic vessel density, and CAF abundance (fibroblast activation protein α (FAP-α) positivity).

Dachsous1-Fat4 Signaling Controls Endothelial Cell Polarization During Lymphatic Valve Morphogenesis-Brief Report.

OBJECTIVE: The purpose of this study was to investigate the role of Fat4 and Dachsous1 signaling in the lymphatic vasculature. APPROACH AND RESULTS: Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1. The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1high [prospero homeobox protein 1] cells) are disoriented and failed to form proper valve leaflets. Using Lifeact-GFP (green fluorescent protein) mice, we revealed that va

Histomorphometric evaluation of the Ki-67 proliferation rate and CD34 microvascular and D2-40 lymphovascular densities drives the pulmonary typical carcinoid outcome.

Ki-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life ex

YAP1/Piezo1 involve in the dynamic changes of lymphatic vessels in UVR-induced photoaging progress to squamous cell carcinoma.

BACKGROUND: UV-induced cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The constant alterations of the lymp … n (UVR). METHODS: TIMER2.0 was used to analyze whether YAP1/VEGFC signaling pathway is involved in lymphangiogenesis in head and neck squamous cell carcinoma (HNSCC). Meanwhile, lymphatic-centered immune microenvironments alterations and the related cumulative survival time were also analyzed. With the accumulated UVR, skin photoaging developed and gradually progr …

Rictor, an mTORC2 Protein, Regulates Murine Lymphatic Valve Formation Through the AKT-FOXO1 Signaling.

BACKGROUND: Lymphatic valves are specialized structures in collecting lymphatic vessels and are crucial for preventing retrograde lymph flow. Mutations in valve-forming genes have been clinically implicated in the pathology of congenital lymphedema. Lymphatic valves form when oscillatory shear stress from lymph flow signals through the PI3K/AKT pathway to promote the transcription of valve-forming genes that trigger the growth and maintenance of lymphatic valves. Conventionally, in many cell types, AKT is phosphorylated at Ser473 by the mTORC2 (mammalian target of rapamycin complex 2). However

Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling.

RATIONALE: Lymphatic vasculature constitutes a second vascular system essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown. OBJECTIVE: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9β1. However, its physiological function is unclear. Here, we investigated the role of

Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium.

Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and di

Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions.

Lymph nodes (LNs) are important hubs for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites through a series of mechanisms, and it has been proved that lymph node metastasis (LNM) is an essential prognostic indicator in many different types of cancer. Therefore, it is important for oncologists to understand the mechanisms of tumor cells to metastasize to LNs, as well as how LNM affects the prognosis and therapy of patients with cancer in order to provide patients with accurate disease assessment and effective treatment strategies. In recent years

Совпадение в полном тексте источника
… Vascular endothelial growth factor (VEGF)-C and VEGF-D play key roles in the regulation of lymphangiogenesis. … reflects the influence of immune cells on lymphangiogenesis in LNM. …

Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.

Lymphedema is a chronic inflammatory disease without an effective treatment method, and it results in a high disease burden and psychological distress in patients. Although there have been significant advances in targeted therapies, there are still no effective options to treat this refractory disease. In recent years, new advances and breakthroughs have been made in signaling pathways, including RAS/MAPK, PI3K/AKT, VEGF-C/VEGFR-3, HGF/MET, and TGF-β1, which are important for understanding the pathogenesis and disease progression of lymphedema. Mutations in genes encoding cell junctions affect

Совпадение в полном тексте источника
… In summary, the interaction between fibroblasts, particularly CAFs, and LECs plays a significant role in the regulation of lymphangiogenesis. … For example, IL-4 and IL-13, which are secreted by Th2 cells, have been shown to inhibit lymphangiogenesis by inducing LEC apoptosis. In contrast, M2 macrophage polarization has been shown to promote compensatory lymphangiogenesis through the secretion of VEGF-C. …

Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial fo

Совпадение в полном тексте источника
… , suggesting that lymphangiogenesis may be a promising disease treatment prospect [ 106 – 108 ] . … One study found that VEGF-C, the major growth factor that induces lymphangiogenesis, enhanced local lymphatic vessel formation and reversed alveolar bone loss [ 114 ] . …

Role of macrophages in the pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is one of the most common and most intensively studied chronic inflammatory skin diseases. Several cofactors, such as an impaired skin barrier function, modifications of the immune system, and a complex genetic background, direct the course of AD. Within this complex network, macrophages play a pivotal role in enhanced susceptibility to cutaneous infections and act as central connecting components in the pathogenesis of AD on the cellular level. In AD, macrophages are known to accumulate in acutely and chronically inflamed skin. During the early and short inflammatory ph

Совпадение в полном тексте источника
… For instance, Shi et al. [ 89 ] investigated the possible link of macrophages recruitment and lymphangiogenesis in Keratin14-IL-4 Transgenic (Tg) mouse model of AD. … The possible role of lymphangiogenesis in different phenotypes and phases of AD remains elusive. It is likely that better understanding of altered angiogenesis/lymphangiogenesis in different forms and stages of AD may prove beneficial in the treatment of this common inflammatory skin disorder. …