19 research outputs found

    Integrated study of the effects of antiangiogenic therapy on microvascular physiology in human cancer models

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    Molecular imaging of tumor-associated angiogenesis using a novel magnetic resonance imaging contrast agent targeting αvβ3 integrin

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    The recent introduction of biological anticancer therapy has renewed the interest in functional imaging of tumor-associated angiogenesis (TAA) as a tool to monitor early therapy response. The present study evaluated imaging of TAA using P1227, a novel, small molecular magnetic resonance imaging (MRI) probe targeting alpha(v)beta(3) integrin. HT29 human colorectal cancers were grown in athymic mice. Dynamic MRI was performed using a three-dimensional VIBE sequence up to 110 min after injection of P1227 or gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA). Specificity was assessed by using P1227 1 h after intravenous administration of the alpha(v)beta(3) inhibitor cilengitide. Regions of interest were drawn encompassing the tumor rim and normal muscle. Imaging data were compared with microvessel density and alpha(v)beta(3) expression. Using P1227, specific enhancement of the angiogenic tumor rim, but not of normal muscle, was observed, whereas Gd-DOTA enhanced tumor and normal muscle. After administering cilengitide, enhancement with P1227, but not with DOTA, was significantly suppressed during the first 20 min. When using P1227, a significant correlation was observed between normalized enhancement of the tumor rim and immunohistochemical alpha(v)beta(3) integrin expression. Molecular MRI using a small monogadolinated tracer targeting alpha(v)beta(3) integrin and moderate magnetic field strength holds promise in assessing colorectal TAA

    Measuring the nursing workload per shift in the ICU

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    In the intensive care unit (ICU) different strategies and workload measurement tools exist to indicate the number of nurses needed. The gathered information is always focused on manpower needed per 24 h. However, a day consists of several shifts, which may be unequal in nursing workload. The aim of this study was to evaluate if differences in nursing workload between consecutive shifts can be identified by a nursing workload measurement tool. The nursing activities score (NAS) was registered per patient for every shift during a 4-week period in a prospective, observational research project in the surgical-pediatric ICU (SICU-PICU) and medical ICU (MICU) of an academic hospital. The NAS was influenced by the patient characteristics and the type of shift. Furthermore, the scores were lower during night shifts, in weekends and in MICU patients. Overall, the mean NAS per nurse per shift was 85.5 %, and the NAS per 24 h was 54.7 %. This study has shown that the nursing workload can be measured per working shift. In the ICU, the NAS differentiates the nursing workload between shifts, patients and units

    The low-molecular-weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model

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    BACKGROUND: Recently, low-molecular-weight heparins (LMWHs) were found to confer a survival advantage in cancer patients. The mechanism underlying this observation is unclear, but may involve inhibition of tumour angiogenesis. We aimed to examine the effects of nadroparin on tumour angiogenesis using a dorsal skinfold window chamber model in the Syrian hamster. METHODS: AMel-3 and HAP-T1 tumours were grown in donor animals and fragments implanted in the window chambers. Animals (N=46) were treated with 200 IU of nadroparin or saline for 10 days. Repeated intravital fluorescence microscopy was performed to calculate functional microcirculatory parameters: number (N) and length (L) of microvessels, vascular area fraction (AF), and red blood cell velocity (V). Microvessel density (MVD), fractal dimension, and pericyte coverage were assessed histologically. RESULTS: Active angiogenesis was observed in control animals, resulting in a significant increase in N, L, and AF. In nadroparin-treated animals, however, N and L did not increase whereas AF decreased significantly. Both groups showed an initial increase in V, but nadroparin treatment resulted in an earlier decrease in red blood cell velocity over time. Compared with control animals, nadroparin-treated animals showed a significantly lower MVD and fractal dimension but significantly higher pericyte coverage index (PCI). CONCLUSIONS: Taken together, these results suggest that the LMWH nadroparin inhibits tumour angiogenesis and results in microvessel normalisation
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