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Peter Vajkoczy

Publications and source records attributed to Peter Vajkoczy.

30 records · Page 2Linked to original sources
PubMed2004

Moyamoya-like vasculopathy (moyamoya syndrome) in children.

INTRODUCTION: A large variety of inherited or acquired childhood disorders and conditions may present in conjunction with progressive bilateral stenosis and/or occlusion of the terminal segments of the internal carotid artery. In addition, the development of pathological collateral vessels can be observed in the vicinity of the steno-occlusive changes in these patients. This condition is known as moyamoya-like (MML) vasculopathy. The natural history, the angiographic appearance, and the pathology of MML vasculopathy probably differ from those of definite moyamoya disease. Adequate cerebral vascular imaging should be considered in all pediatric patients with inherited or acquired systemic disorders and symptoms attributable to cerebral ischemia. CASES AND DISCUSSION: We present four pediatric cases of MML vasculopathy, and outline the etiology, the current classification, and the therapeutic approaches for this heterogeneous disease entity.

Brain Neoplasms↗
PubMed2004

Vascular microenvironment in gliomas.

Structural and functional abnormalities of the vascular microenvironment determine pathophysiological characteristics of gliomas, such as loss of blood-brain barrier function, tumor cell invasiveness, or permselectivity for large molecules. Moreover, the effectiveness of various therapeutic strategies critically depends upon the successful transvascular delivery of molecules. In order to shed more light on the vascular microenvironment in gliomas, a variety of experimental and clinical techniques have been applied to study the glioma microvasculature, including histology, vascular corrosion casts, microangiography, autoradiography, tracer washout techniques, magnetic resonance imaging, as well as intravital fluorescence microscopy. This review summarizes the characteristic features of vascular morphology, angio-architecture, tumor perfusion, microvascular permeability, and microvessel-related immunological competence in gliomas. An improved understanding of the vascular microenvironment in gliomas will help in the future to optimize glioma imaging and to improve delivery of vectors for gene therapy or encapsulated drug carriers for pharmacotherapy in patients.

Animals↗
PubMed2004

Liver regeneration in FGF-2-deficient mice: VEGF acts as potential functional substitute for FGF-2.

BACKGROUND/AIMS: The angiogenic properties, its role in mesoderm differentiation and cell culture studies implicate an important role of fibroblast growth factor (FGF-2) in liver regeneration. The aim of the study was to evaluate this role in a FGF-2 knockout mouse model. METHODS: Liver regeneration after left hemihepatectomy (partial hepatectomy, PH) was evaluated in homozygous FGF-2 deficient (-/-) mice (male C57BL/6J) and their FGF-2 competent (+/+) littermates (controls) (day 0-10). RESULTS: FGF-2-(-/-) mice displayed normal dynamics in liver regeneration. FGF-2 protein was overexpressed 4 days post PH in controls. BrdU incorporation showed a biphasic pattern in FGF-2-(-/-) mice, whereas it decreased continuously after one peak (day 2) in controls. In FGF-2-(-/-) livers hepatic growth factor mRNA post PH was 1 day longer decreased and markedly less elevated thereafter compared with control. Vascular endothelial growth factor (VEGF) mRNA levels were clearly increased in FGF-2-(-/-) mice pre- and postoperatively in contrast to controls. VEGF protein levels in livers of FGF-2-(-/-) mice were elevated preoperatively, but similar in both groups after PH. With SU5416, a VEGF-receptor inhibitor, liver regeneration in FGF-2-(-/-) mice was reduced significantly, whereas it remained unchanged in controls. CONCLUSIONS: Liver regeneration dynamics in FGF-2-(-/-) mice were comparable with controls, potentially due to a functional substitution of FGF-2 by VEGF.

Angiogenesis Inhibitors↗
PubMed2003

Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms.

Destruction of existing tumor blood vessels may be achieved by targeting vascular endothelial growth factor (VEGF) signaling, which mediates not only endothelial cell proliferation but also endothelial cell survival. In this study, however, intravital microscopy failed to demonstrate that targeting of VEGFR-2 (by the tyrosine kinase inhibitor SU5416) induces significant regression of experimental tumor blood vessels. Immunohistochemistry, electron microscopy, expression analyses, and in situ hybridization provide evidence that this resistance of tumor blood vessels to VEGFR-2 targeting is conferred by pericytes that stabilize blood vessels and provide endothelial cell survival signals via the Ang-1/Tie2 pathway. In contrast, targeting VEGFR-2 plus the platelet-derived growth factor receptor (PDGFR)-beta system (PDGFR-beta) signaling (by SU6668) rapidly forced 40% of tumor blood vessels into regression, rendering these tumors hypoxic as shown by phosphorescence quenching. TUNEL staining, electron microscopy, and apoptosis blocking experiments suggest that VEGFR-2 plus PDGFR-beta targeting enforced tumor blood vessel regression by inducing endothelial cell apoptosis. We further show that this is achieved by an interference with pericyte-endothelial cell interaction. This study provides novel insights into the mechanisms of how 1) pericytes may provide escape strategies to anti-angiogenic therapies and 2) novel concepts that target not only endothelial cells but also pericyte-associated pathways involved in vascular stabilization and maturation exert potent anti-vascular effects.

Animals↗
PubMed2003

Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis.

Tissue neovascularization involves recruitment of circulating endothelial progenitor cells that originate in the bone marrow. Here, we show that a class of embryonic endothelial progenitor cells (Tie-2+, c-Kit+, Sca-1+, and Flk-1-/low), which were isolated at E7.5 of mouse development at the onset of vasculogenesis, retain their ability to contribute to tumor angiogenesis in the adult. Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation. Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks. Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1. This paper provides the first in vivo insights into the mechanisms of endothelial progenitor cell recruitment and, thus, indicates novel ways to interfere with pathological neovascularization.

Animals↗
PubMed2003

Blockade of in vivo VEGF-KDR/flk-1 signaling does not affect revascularization of freely transplanted pancreatic islets.

BACKGROUND: The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) binding to its high-affinity receptor kinase insert domain (KDR)-containing receptor/fetal liver kinase (flk)-1 in mediating revascularization of freely transplanted pancreatic islets in vivo. METHODS: Isolated pancreatic islets were syngeneically transplanted into dorsal skinfold chambers of Syrian hamsters. Animals were treated daily with the VEGF-KDR/flk-1 antagonist SU5416 (25 mg/kg intraperitoneally) or received vehicle for control. Intravital fluorescence microscopy and computer-assisted off-line analysis were used to study islet graft angiogenesis and revascularization during days 6, 10, and 14 after transplantation. RESULTS: In controls, islets were revascularized within 10 to 14 days after transplantation. SU5416 treatment did not affect revascularization, inasmuch as both functional capillary density and size of revascularized endocrine tissue did not differ from that of vehicle-treated controls. CONCLUSION: Because blockade of VEGF-KDR/flk-1 function does not affect islet revascularization, we conclude that VEGF signaling through its high-affinity receptor KDR/flk-1 is not an essential prerequisite for the process of new-vessel formation in freely transplanted islets of Langerhans.

Animals↗
PubMed2003

pO(2) measurements by phosphorescence quenching: characteristics and applications of an automated system.

An automated system for pO(2) analysis based upon phosphorescence quenching was tested. The system was calibrated in vitro with capillary samples of saline and blood. Results were compared to a conventional measuring procedure wherein pO(2) was calculated off-line by computer fitting of phosphorescence decay signals. PO(2) measurements obtained by the automated system were correlated (r(2) = 0.98) with readings simultaneously generated by a blood gas analyzer, accuracy being highest in the low (0-20 mm Hg) and medium pO(2) ranges (21-70 mm Hg). Measurements in in vivo studies in the hamster skin-fold preparation were similar to previously reported results. The automated system fits the phosphorescence decay data to a single exponential and allows repeated pO(2) measurements in rapid sequence.

Animals↗
PubMed2003

Regional cerebral blood flow monitoring in the diagnosis of delayed ischemia following aneurysmal subarachnoid hemorrhage.

OBJECT: The goal of this study was to evaluate regional cerebral blood flow (rCBF) monitoring, performed using thermal-diffusion (TD) flowmetry, as a novel means for the bedside diagnosis of symptomatic vasospasm. METHODS: Fourteen patients with high-grade subarachnoid hemorrhage (SAH) who underwent early clip placement for anterior circulation aneurysms were prospectively entered into the study. Thermal-diffusion microprobes were implanted into the white matter of vascular territories that were deemed at risk for developing symptomatic vasospasm. Data on arterial blood pressure, intracranial pressure, cerebral perfusion pressure, rCBF measurement obtained using a TD probe (TD-rCBF), cerebrovascular resistance (CVR), and blood flow velocities were collected at the patient's bedside. The diagnosis of symptomatic vasospasm was based on the manifestation of a delayed ischemic neurological deficit and/or a reduced territorial level of CBF as assessed using stable Xe-enhanced computerized tomography (CT) scanning in combination with vasospasm demonstrated by angiography. Bedside monitoring of TD-rCBF and CVR allowed the detection of symptomatic vasospasm. In the 10 patients with vasospasm the TD-rCBF decreased from 21 +/- 4 to 9 +/- 1 ml/100 g/min (mean +/- standard error of the mean), whereas in the four other patients the TD-rCBF value remained unchanged (mean TD-rCBF = 25 +/- 4 compared with 21 +/- 4 m/100 g/min). A comparison of the results of TD-rCBF and Xe-enhanced CT studies, as well as the calculation of sensitivities, specificities, predictive values, and likelihood ratios, identified a TD-rCBF value of 15 ml/100 g/min as a reliable cutoff for the diagnosis of symptomatic vasospasm. In addition, TD flowmetry was characterized by a more favorable diagnostic reliability than transcranial Doppler ultrasonography. CONCLUSIONS: Thermal-diffusion flowmetry represents a promising method for the bedside monitoring of patients with SAH to detect symptomatic vasospasm. This is of major clinical interest for patients with high-grade SAH, who often cannot be assessed neurologically.

Adolescent↗
PubMed2002

Encephalitogenic T cells use LFA-1 for transendothelial migration but not during capture and initial adhesion strengthening in healthy spinal cord microvessels in vivo.

LFA-1 on the surface of encephalitogenic T cells has been suggested to be involved in the pathogenesis of experimental autoimmune encephalomyelitis. By applying a novel technique of intravital fluorescence microscopy that enables us to visualize the interaction of circulating encephalitogenic T lymphoblasts within the healthy spinal cord white matter microvasculature in vivo, we investigated the possible involvement of LFA-1 on circulating encephalitogenic T cells in their multi-step interaction with the blood-brain barrier endothelium in vivo. LFA-1 was found to mediate neither the G-protein-independent capture nor the G-protein-dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessels. In contrast, blocking of LFA-1 on encephalitogenic T lymphoblasts resulted in a significantly reduced number of T cells firmly adhering within spinal cord microvessels 2 h after injection and in a significantly reduced number of T cells subsequently migrating across the vascular wall into the spinal cord parenchyme. Our study provides the first direct evidence that encephalitogenic T cells use LFA-1 for transendothelial migration but not for capture and initial adhesion in spinal cord microvessels in vivo.

Animals↗
PubMed2002

Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2.

Tumors have been thought to initiate as avascular aggregates of malignant cells that only later induce vascularization. Recently, this classic concept of tumor angiogenesis has been challenged by the suggestion that tumor cells grow by co-opting preexisting host vessels and thus initiate as well-vascularized tumors without triggering angiogenesis. To discriminate between these two mechanisms, we have used intravital epifluorescence microscopy and multi-photon laser scanning confocal microscopy to visualize C6 microglioma vascularization and tumor cell behavior. To address the mechanisms underlying tumor initiation, we assessed the expression of VEGF, VEGF receptor-2 (VEGFR-2), and angiopoietin-2 (Ang-2), as well as endothelial cell proliferation. We show that multicellular aggregates (<< 1 mm(3)) initiate vascular growth by angiogenic sprouting via the simultaneous expression of VEGFR-2 and Ang-2 by host and tumor endothelium. Host blood vessels are not co-opted by tumor cells but rather are used as trails for tumor cell invasion of the host tissue. Our data further suggest that the established microvasculature of growing tumors is characterized by a continuous vascular remodeling, putatively mediated by the expression of VEGF and Ang-2. The results of this study suggest a new concept of vascular tumor initiation that may have important implications for the clinical application of antiangiogenic strategies.

Angiopoietin-2↗