Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding

Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase transmembrane receptor that has also a soluble isoform containing most of the extracellular ligand binding domain (sVEGFR-1). VEGF-A binds to both VEGFR-2 and VEGFR-1, whereas placenta growth factor (PlGF) interacts exclusively with VEGFR-1. In this study we generated an anti-VEGFR-1 mAb (D16F7) by immunizing BALB/C mice with a peptide that we had previously reported to inhibit angiogenesis and endothelial cell migration induced by PlGF. D16F7 did not affect binding of VEGF-A or PlGF to VEGFR-1, thus allowing sVEGFR-1 to act as decoy receptor for these growth factors, but it hampered receptor homodimerization and activation. D16F7 inhibited both the chemotactic response of human endothelial, myelomonocytic and melanoma cells to VEGFR-1 ligands and vasculogenic mimicry by tumor cells. Moreover, D16F7 exerted in vivo antiangiogenic effects in a matrigel plug assay. Importantly, D16F7 inhibited tumor growth and was well tolerated by B6D2F1 mice injected with syngeneic B16F10 melanoma cells. The antitumor effect was associated with melanoma cell apoptosis, vascular abnormalities and decrease of both monocyte/macrophage infiltration and myeloid progenitor mobilization. For all the above, D16F7 may be exploited in the therapy of metastatic melanoma and other tumors or pathological conditions involving VEGFR-1 activation

Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats

The aim of this study was to examine oxidative load and endothelium-dependent vasorelaxation in the serotonin pre-constricted femoral artery (FA) of Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding in the presence or absence of ascorbic acid (AsA) in working solution. Adult male rats were randomly divided into control (living space: 480 cm2/rat) or stressed (living space: 200 cm2/rat) groups for 8 weeks. Blood pressure and heart rate, determined using tail-cuff plethysmography, were not influenced by stress vs. control. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured in the left ventricle and liver (for assessment of oxidative load) and were found unchanged by chronic crowding. The nitric oxide (NO)-dependent component of endothelium-dependent relaxation was investigated in the FA using a wire myograph. In both the presence and absence of AsA, acetylcholine-induced relaxation of the FA of stressed rats significantly exceeded that of the controls, which was associated with an increase of the NO-dependent component. In conclusion, the data showed that chronic crowding did not produce oxidative stress in the organs investigated and indicate that elevation of NO production during chronic stress is an important way of adaptation, which may prevent normotensive rats from the development of stress-induced hypertension

UST2/475: Are Parents Appreciating Medical Web Sites? Results from an Italian survey

[This item is a preserved copy and is not necessarily the most recent version. To view the current item, visit http://www.jmir.org/1999/suppl1/e128/ ] Introduction: The growth of the number of Internet users leads to an increasing demand for information quality control, especially when information is not oriented to healthcare professionals but to patients and/or general citizens. Even if several surveys have been done to evaluate the kind of access to medical information the relevance of this phenomenon in the families does not seems adequately investigated. In fact navigators (see Oct.98 GVU survey) are mainly (70%) without sons and access to medical information over fifty. The goal of this research is to evaluate the number and characteristics of Italian parents that could be interested to medical webs. This study is the first step to the main goal of evaluating paediatrics information quality provided by Web sites aimed to educate parents. Methods: The survey, done in two Italian cities, involved 284 families having access to a Internet, and responding to questionnaires distributed and collected (May 24th to June 10th) mainly in primary schools. Parents were asked to answer about the frequency and location of access, whether they visited medical sites and the usefulness of them. To evaluate its readability and to select the size of the sample, this questionnaire was tested with 79 parents, during a one week pilot phase carried out in the outpatient paediatrics department of Policlinico A. Gemelli, Rome. To respect data privacy, questions about sensible personal data were not included and it was filled in an anonymous way. RESULTS: The characteristics of the sample are the following ones.-41% have higher school education and 56% are graduated. -65% are employees and 28% are free-lance. -the average age for the fathers is 42.8 years (29 to 58) and for the mothers is 39.7 years (28 to 53); -48% are mothers and 52% are fathers;-the majority of families (53%) has 2 sons and 31% of them has 1 son. The usage of internet shows the following Results: 10% connect mainly from both office and home, 56% connect mainly from the office, and 29% mainly from home 25% has a daily connection, 34% more than once a week, 17% less than once a week and 16% once a month 35% has visited medical sites (40% of the fathers and 31% of the mothers) and, among them, 56% found medical sites useful and 26% very useful Discussion: The usage of Internet at home is less frequent than from the office: this shows the minor diffusion of Internet in the Italian homes, probably because of the high communication costs. A very interesting result is the high number of internet users accessing medical sites (about one third); furthermore the great majority of the parents navigating through medical sites find this information useful or very useful. Another interesting results is the fact that our survey shows a greater interest in medical sites from fathers with respect to mothers (GVU survey stated a greater and more frequent access of women to medical information)