Publications (6)33.38 Total impact
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Article: Investigation of circulating endothelial progenitor cells and angiogenic and inflammatory cytokines during recovery from an episode of major depression.
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ABSTRACT: Epidemiological studies strongly suggest a bidirectional positive relationship between mood and cardiovascular disorders (CVD). Reduced numbers of circulating endothelial progenitor cells (cEPCs) are associated with elevated risks of CVD. Previously we demonstrated that patients with a current episode of major depression (MDE) have a decreased number of cEPCs. The role of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF) has been demonstrated in the etiopathogenesis of depression. In addition these cytokines are also involved in regulation of the vascular system. This suggests that VEGF and/or TNF may also mediate the elevated risk of CVD associated with mood disorders. In the current investigation, which has a self-controlled study design, we examined changes in VEGF and TNF levels and--for the first time--changes in cEPC number during recovery from MDE. Twenty-four patients with MDE were enrolled. The severity of their depressive symptoms improved significantly during the one-month treatment period (~50% decrease in MADRS score; P≤0.001). We did not find significant differences between baseline and end-point levels of VEGF, TNF and the number of cEPCs. Our negative result for alteration in the number of cEPCs in the course of recovery from MDE raises several questions. Before discarding the number of cEPCs as a possible marker of depression--and/or elevated CV risk associated with it--our results would require confirmation in larger samples. Our results for TNF and VEGF do not contradict the findings of prior studies, since these were controversial.Journal of affective disorders 02/2012; 136(3):1159-63. · 3.76 Impact Factor -
Article: Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis.
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ABSTRACT: The recently discovered bioactive peptide, apelin, has been demonstrated to stimulate angiogenesis in various experimental systems. However, its clinical significance and role in tumor vascularization have not yet been investigated in a human malignancy. Therefore, our aim was to study whether apelin expression is associated with angiogenesis and/or tumor growth/behavior in human non-small cell lung cancer (NSCLC). A total of 94 patients with stage I-IIIA NSCLC and complete follow-up information were included. Apelin expression in human NSCLC samples and cell lines was measured by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Effects of exogenous apelin and apelin transfection were studied on NSCLC cell lines in vitro. In vivo growth of tumors expressing apelin or control vectors were also assessed. Morphometric variables of human and mouse tumor capillaries were determined by anti-CD31 labeling. Apelin was expressed in all of the six investigated NSCLC cell lines both at the mRNA and protein levels. Although apelin overexpression or apelin treatments did not increase NSCLC cell proliferation in vitro, increasing apelin levels by gene transfer to NSCLC cells significantly stimulated tumor growth and microvessel densities and perimeters in vivo. Apelin mRNA levels were significantly increased in human NSCLC samples compared with normal lung tissue, and high apelin protein levels were associated with elevated microvessel densities and poor overall survival. This study reveals apelin as a novel angiogenic factor in human NSCLC. Moreover, it also provides the first evidence for a direct association of apelin expression with clinical outcome in a human cancer.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2010; 5(8):1120-9. · 4.55 Impact Factor -
Article: Differential inhibition of single and cluster type tumor cell migration.
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ABSTRACT: For the control of tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of HT-1080 fibrosarcoma cells and OSCORT osteosarcoma cells was compared in a Boyden chamber and in an extracellular matrix (ECM)-based three-dimensional cell culture (3-DCC) model system. The Boyden chamber offers a model of single tumor cell migration, whereas the 3-DCC model system demonstrates invasive growth in the form of a cluster. Since PD98059 (MEK inhibitor) exclusively reduced migration in the 3-DCC model, it may be plausible that the ERK/MAPK signaling pathway is essential for cluster type migration. Interestingly, single cell migration was stimulated upon blocking phosphatidylinositol 3-kinase (PI3K) and also p38-MAPK by treatment with LY294002 and SB203580 respectively. A remarkable reduction of single cell migration was observed following treatment with okadaic acid, a phosphatase 1 (PP1) and 2A (PP2A) inhibitor, which was rather intriguing. This study provided evidence that certain cytotoxic/cytostatic agents at appropriate concentrations were able to preferentially inhibit certain types of migration relative to cell proliferation. Single cell migration was selectively inhibited by taxol at very low subtoxic concentration, whereas 5-hexyl-2'-deoxyuridine (HUdR) exclusively inhibited the cluster type of migration. The borrelidin compound was able to inhibit both types of tumor cell migration, but single tumor cell migration was much less affected. It is interesting that migration was more reduced than proliferation by borrelidin, especially at the advanced growth stage. Taxol is recommended as an agent acting against single cell migration, as well as HUdR and borrelidin as leading compounds for developing antimetastatic drugs against cluster type migration.Anticancer research 09/2009; 29(8):2981-5. · 1.73 Impact Factor -
Article: High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer.
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ABSTRACT: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P<0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P<0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P<0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P<0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.Clinical Cancer Research 03/2009; 15(5):1741-6. · 7.74 Impact Factor -
Article: Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer.
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ABSTRACT: Until recently, it was generally accepted that vascularization of tumors arises exclusively from endothelial sprouting. Whether circulating bone marrow-derived endothelial progenitor cells (EPC) participate in the progression of non-small cell lung cancer (NSCLC) has not yet been evaluated. EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood of 53 NSCLC patients. Furthermore, by means of a quantitative reverse transcription-PCR approach, we measured VEGFR2, CD133, CD34, and VE-cadherin mRNA in the peripheral blood samples of the same patient population. EPCs in tumor samples were identified by confocal microscopy using CD31, CD34, CD133, and VEGFR2 antibodies. Although immunofluorescent labeling of microvessels made clear that incorporation of EPCs is a rare phenomenon in NSCLC tissue (9 of 22 cases), circulating EPC levels before therapeutic intervention were increased in NSCLC patients (P < 0.002, versus healthy controls), and high pretreatment circulating EPC numbers correlated with poor overall survival (P < 0.001). Furthermore, in the subgroup of responders to treatment, the posttreatment EPC numbers in the peripheral blood were significantly lower compared with nonresponding patients. Interestingly, pretreatment mRNA levels of CD133, VE-cadherin, and CD34 were not significantly increased in NSCLC patients, whereas VEGFR2 expression was increased by 80-fold. Moreover, posttreatment VEGFR2 mRNA level in the peripheral blood was significantly higher in the subgroup of nonresponding patients when compared with posttreatment level of patients responding to antitumor therapy. Circulating levels of bone marrow-derived EPCs are significantly increased in NSCLC patients and correlate with clinical behavior.Cancer Research 07/2006; 66(14):7341-7. · 7.86 Impact Factor -
Article: Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer.
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ABSTRACT: Recent experimental studies have revealed that lymphangiogenesis plays an important role in cancer progression, but its clinical significance in the case of non-small cell lung cancer (NSCLC) remains unclear. Our aim was to assess the lymphangiogenesis of human NSCLC, and to correlate this with angiogenic phenotype (angiogenic versus nonangiogenic growth pattern) and clinical behavior. One hundred and three patients with NSCLC and complete follow-up information were included. Tumor samples were immunostained for vascular endothelial growth factor-C (VEGF-C), the lymphatic endothelial markers, LYVE-1 and D2-40/Podoplanin, and the panvascular marker, CD31. Lymphatic vessel density (LVD) and perimeters were evaluated within the tumor and peritumorally. LVDs at the tumor periphery were significantly higher in lymph node metastatic tumors (P < 0.005) and high LVDs correlated with poor overall survival (P < 0.001). However, this tendency proved to be significant only in the angiogenic tumor group (P < 0.001). Although 68% of the patients with nonangiogenic tumors had lymph node metastasis (P = 0.0048 versus angiogenic tumors), in the patient group with nonangiogenic NSCLCs, there was no information from the LVDs in any investigated tumor area (P > 0.05). In contrast to angiogenic tumors, which had actively sprouting lymphatics in all of the investigated tumor areas, nonangiogenic tumors showed no Ki67 staining intratumorally. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in NSCLC. Moreover, it also provides the first evidence that nonangiogenic NSCLCs mainly co-opt host tissue lymphatics during their growth, in contrast to most of the angiogenic tumors, which expand with concomitant lymphangiogenesis.Clinical Cancer Research 10/2005; 11(20):7344-53. · 7.74 Impact Factor
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2010
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Medical University of Vienna
Vienna, Vienna, Austria
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