Poorly synchronized activation of the ventricles can lead to impairment of normal cardiac structure/function. We previously reported that short term (4 hr) LV pacing induced ventricular dyskinesis led to an inflammatory response localized to the epicardium. Results from this study demonstrated that neutrophils may play a major role in this ...

Markers of inflammation have previously been related to left ventricular (LV) hypertrophy (LVH) in uremic and hypertensive patients. The present study investigated inflammatory markers in relation to LV geometry and diastolic function in a population of elderly persons. In the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) ...

BACKGROUND: Livedoid vasculopathy (LV) is a disease characterized by multiple painful and recurrent ulcerations on the feet, accompanied by atrophic scars. Many researchers suggest that a hypercoagulable status is the pathogenetic factor for LV. However, the cause of LV remains elusive. OBJECTIVE: We sought to determine if endothelial dysfunction is ...

Aims The intercalated disc (ID) contains two complexes, adhesion junction (AJ) and gap junction (GJ). We studied the ID remodeling and its potential role in the arrhythmogenesis, and investigated the effects of olmesartan on ID remodeling during development of heart failure (HF) in UM-X7.1 cardiomyopathic hamster (UM-X7.1). Methods and Results ...

Proprotein convertase (PC) 5/6 belongs to a family of secretory proteases involved in proprotein proteolysis. Several studies suggest a role for PC5/6 in cardiovascular disease. Because lethality at birth of mice lacking PC5/6 precluded elucidation of its function in the adult, we generated mice in which the gene of PC5/6 ...

Homotypic cell adhesion is fundamental to the maintenance of cell and tissue structure and function and is predominantly mediated by cadherin-containing adherens junction complexes. The integrity of these adhesion sites can be modulated by Src, a non-receptor tyrosine kinase implicated in the development and progression of a number of tumour ...

Vascular endothelial growth factor C (VEGF-C) is a key regulator of angiogenesis and lymphangiogenesis. VEGF-C is also implicated in the development of esophageal cancer. We investigated the mRNA levels of VEGF-C and its receptors in 38 esophageal squamous cell carcinoma specimens (ESCCs) and matched adjacent normal esophageal tissues via real-time ...

Aquaporins play important roles in water and glycerol transport. We examined whether aquaporin 3 (AQP3) is expressed in primary squamous cell carcinoma (SCC) such as esophageal and oral cancer and lymph node metastasis, and whether AQP3 is a potential target for tumor therapy. A high level expression of AQP3 was ...

BACKGROUND: Esophageal adenocarcinoma is an aggressive malignancy, with most patients succumbing to metastatic disease. The presence of intercellular adhesion molecule-1 (ICAM-1) in these cancer cells contributes to their metastatic potential. The ICAM-1 production in other cell types is stimulated by the actions of phospholipase enzymes. We hypothesize that inhibition of ...

Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study 59 paediatric pilocytic astrocytomas were compared with 62 ...

Angiogenesis plays an essential role in the growth and metastasis of esophageal carcinoma. Vascular endothelial growth factor, thymidine phosphorylase, fibroblast growth factor, midkine, and hepatocyte growth factor have been reported to be vital molecules for tumor angiogenesis. Polymorphisms in gene encoding angiogenic factors or their receptors may alter protein expression ...

Testicular germ cell tumours (TGCTs) represent about 2% of male malignancies, being the most common cancer among adolescents and young adults. As in most neoplasias, TGCTs show a chaotic vascular architecture, altered blood supply and over-expression of pro-angiogenic factors, aspects closely related to tumour overgrowth and metastasis. Following this trend, ...

The natural flavonoid fisetin was recently identified as a lead compound that stabilizes endothelial cell microtubules. In this study, we investigated the antiproliferative and antiangiogenic properties of fisetin in vitro and in vivo. Fisetin cytotoxicity was evaluated using Lewis lung carcinoma cells (LLC), endothelial cells and NIH 3T3 cells. Endothelial ...

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. Tumour-associated endothelium offers an additional mechanism for enhanced viral uptake into tumours which is accessible for systemic gene delivery. Building on expertise in using polymer 'stealthed' viruses for targeting in vivo, adenovirus expressing luciferase (Adluc) was ...

Transmembrane proteins of the tetraspanin superfamily are implicated in a broad spectrum of cellular processes in many biological systems in both health and disease. Tetraspanins form specialized membrane microdomains on the cell surface which control cell proliferation and migration through various adhesion and growth factor receptors. Recent extensive research has ...

Vascular endothelial-derived growth factor (VEGF) plays a fundamental role in the formation of new vessels within the tumour mass. Increasing evidence has highlighted the involvement of Toll-like receptors (TLRs) in cancer. Of interest, TLR9 is over-expressed in human lung carcinoma tissues. The aim of our study was to determine whether ...

Angiogenesis plays a crucial role in tumour growth, invasion and metastasis. Mast cells (MCs) release angiogenic factors that promote endothelial proliferation and differentiation. Previous studies have suggested that MCs are involved in tumour angiogenesis due to the release of various pro-angiogenic factors. This study evaluated samples from 40 canine mammary ...

In this work we studied the functional differences between the microcirculation of murine tumours that express only single isoforms of vascular endothelial growth factor-A (VEGF), namely VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin ...

The fact that growth and spread of tumours are dependent on angiogenesis has led to the investigation of the role of anti-angiogenic agents in the therapeutic strategies for thoracic tumours such as nonsmall cell lung cancer or mesotheliomas. Since various angiogenic factors may contribute to the regulation of angiogenesis in ...

Vascular endothelial growth factor (VEGF) is a key player in neo-angiogenesis; it sustains the progression of solid neoplasias, brain tumours included. It has recently been demonstrated that the use of antidepressants correlates with increasing VEGF levels in the central nervous system (CNS). In order to elucidate whether the most used ...

Harmine is a beta-carboline alkaloid present in medicinal plants such as Peganum harmala that have been used as folk medicine in anticancer therapy. In this study, we demonstrated the anti-angiogenic activity of harmine using in vivo and in vitro assay systems. In vivo anti-angiogenic activity was studied using B16F-10 melanoma ...

A 5-year-old female degu (Octodon degus ) showed the clinical sign of metrorrhagia. During ovariohysterectomy a circumscribed tumoural lesion was found in the right uterine horn. The histopathological diagnosis of this soft tissue mass was primary benign cavernous angioleiomyoma of the uterus. During immunohistochemical analysis the neoplastic endothelial cells of ...

BACKGROUND: Bevacizumab is a specific inhibitor of angiogenesis and a neutralising antibody against vascular endothelial growth factor (VEGF). The effect of bevacizumab was evaluated on malignant fibrous histiocytoma (MFH) in vivo using an animal model. MATERIALS AND METHODS: MFH cell line, NaraH, was implanted to athymic nude mice which were ...

Study Type - Aetiology (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known about the impact of vascular ageing on the angiogenic features of clear cell renal cell carcinoma, a disease in which antiangiogenic therapy currently has a well established ...

In this study, the extent of angiogenesis, evaluated as microvascular volume density, immunoreactivity of tumour cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human primary melanoma specimens. Results showed that Epo/EpoR expression correlate with angiogenesis and tumour thickness. These findings suggest that ...

BACKGROUND: Tumour angiogenesis is crucially dependent on the communication between the tumour and the associated endothelium. Protein kinase D (PKD) isoenzymes mediate vascular endothelial growth factor-A (VEGF-A) induced endothelial cell proliferation and migration and are also highly expressed in various tumours. AIM: To examine the role of PKDs for tumour ...

Angiopoietins (ANGPTs) are ligands of the endothelial cell receptor TIE2 and have crucial roles in the tumour angiogenic switch. Increased expression of ANGPT2 relative to ANGPT1 in tumours correlates with poor prognosis. The biological effects of the ANGPT-TIE system are context dependent, which brings into question what the best strategy ...

Matrix metalloproteinases (MMPs) have been implicated in lung cyst formation in lymphangioleiomyomatosis (LAM). As doxycycline inhibits MMP activity in vivo, some patients take doxycycline, as one report has suggested a possible benefit in LAM. However, there have been no randomized controlled clinical trials of doxycycline for LAM, and any mechanism ...

The histopathological and clinical aspects of canine mammary tumours (CMTs) have been widely studied, but the variation in the biological behaviour of these neoplasms hampers the identification of prognostic factors. Sustained angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process ...

Infantile haemangiomas, common benign vascular tumours of childhood, are characterized by rapid growth during the first year of life and a slow regression that is usually completed at 7-10 years of age. These tumours are composed of endothelial cells with high mitotic rates and stromal components such as fibroblasts, mast ...

Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1alpha (HIF-1alpha), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Of the four identified PHD enzymes, PHD2 is considered to be the key oxygen sensor, as knockdown of ...

Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85-90% regress spontaneously, some may become life- or function-threatening and require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, alpha-interferon or ...

BACKGROUND: The importance of angiogenesis in solid tumour growth is well recognised. Tumour angiogenesis is considered the result of an imbalance between pro- and anti-angiogenic factors produced by both the malignancy and normal cells. Endoglin (CD105) is a proliferation-associated, hypoxia-inducible glycoprotein that seems to be clinically superior to other pan-endothelial ...

Glioblastoma is one of the most angiogenic human tumours and endothelial proliferation is a hallmark of the disease. A better understanding of glioblastoma vasculature is needed to optimize anti-angiogenic therapy that has shown a high but transient efficacy. We analysed human glioblastoma tissues and found non-endothelial cell-lined blood vessels that ...

Tumour angioneogenesis is associated with the reexpression of oncofetal fibronectin (oncFn) and tenascin-C (oncTn-C) splice variants, which may serve as targets for antibody-based pharmacodelivery. Knowledge of the vascular distribution and organization in different tumours is of importance for the understanding of tumour vessel formation and might be crucial for therapy. ...

Vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE-2) appear to play a critical role in tumour neovascularization. In this study, we have investigated the expression of VEGF and PGE-2 in 53 canine cutaneous mast cell tumours (MCTs). Immunohistochemistry of tissue sections revealed that VEGF and PGE-2 were expressed in ...

Endocan plays a role in tumour angiogenesis and tumour growth. The aim of this study was to detect the expression of endocan in hepatocellular carcinoma (HCC) tumour-associated endothelial cells and to correlate endocan expression with clinicopathological parameters and tumour angiogenesis. Tumour tissues and surrounding non-cancerous hepatic parenchyma from 42 primary ...

Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy. However, the potential side effects of blocking this pathway remain uncertain. Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising important safety concerns.

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active ...

Laminins are expressed highly in blood vessel basement membranes and have been implicated in angiogenesis. alpha6beta1- and alpha6beta4-integrins are major receptors for laminins in endothelial cells, but the precise role of endothelial alpha6-integrin in tumour angiogenesis is not clear. We show that blood vessels in human invasive ductal carcinoma of ...

Increased levels of circulating VEGF-A have been demonstrated in patients with non-Hodgkin lymphoma (NHL) and are associated with progressive disease and poor clinical outcome. We investigated the role of VEGF-A in lymphoma tumour growth on a molecular level in order to identify the mechanism of VEGF-A-promoted tumour growth and to ...

Neuropilin-1 (NRP1) is a non-tyrosine kinase receptor for vascular endothelial growth factor (VEGF) recently implicated in tumour functions. In this study we used a specific antagonist of VEGF binding to the NRP1 b1 domain, EG3287, to investigate the functional roles of NRP1 in human carcinoma cell lines, non-small-cell lung A549, ...

Secreted protein acidic and rich in cysteine (SPARC), a matricellular glycoprotein, modulates cellular interaction with the extracellular matrix and is capable of altering the growth of various cancers. We therefore sought to determine the effect of SPARC expression on medulloblastoma tumour growth and angiogenesis. To this extent, we selected three ...

Solid tumour growth is dependent on the development of an adequate blood supply. For years, sprouting angiogenesis has been considered an exclusive mechanism of tumour vascularization. However, over the last years, several other mechanisms have been identified, including vessel-co-option, intussusception, recruitment of endothelial precursor cells (EPCs) and even mechanisms that ...

Angiogenesis and haemostasis are closely linked within tumours with many haemostatic proteins regulating tumour angiogenesis. Indeed we previously identified a fragment of human fibrinogen, fibrinogen E-fragment (FgnE) with potent anti-angiogenic properties in vitro and cytotoxic effects on tumour vessels in vivo. We therefore investigated which region of FgnE was mediating ...

The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 ...

BACKGROUND/AIMS: The cytotoxic agent paclitaxel and the anti-resorptive drug zoledronic acid are used in the early and advanced breast cancer setting, respectively. Both agents have been demonstrated to have anti-tumour and anti-endothelial actions. Combining paclitaxel with zoledronic acid induces a synergistic increase in apoptotic breast cancer cell death in vitro, ...

AIMS: In kidney cancer, new anti-angiogenic therapies have emerged requiring parameters of effectiveness. The aim was to analyse the expression of endocan or endothelial cell-specific molecule-1, which is a proteoglycan up-regulated in presence of pro-angiogenic factors. METHOD AND RESULTS: We investigated 44 renal clear cell carcinomas (RCC) and 25 papillary ...

Tumour angiogenesis, described by Folkman in the early seventies, is an essential, complex, and dynamic process necessary for the growth of all solid tumours. Among the angiogenic factors secreted by the tumour cells, the Vascular Endothelial Growth Factor (VEGF) is one of the most important. Most types of human cancer ...

IL-17B is a member of the IL-17 cytokine family which have been implicated in inflammatory response and autoimmune diseases such as rheumatoid arthritis. The founding member of this family, IL-17 (or IL-17A), has also been implicated in promoting tumour angiogenesis through the induction of other proangiogenic factors. Here we examine ...