ALBERT

Beschreibung: Malignant tumors are hypothesized to harbor small populations of self-renewing cancer stem cells. Targeting these cells may be the decisive step to overcome treatment resistance and achieve tumor eradication in cancer patients. Advanced soft tissue sarcomas (STS) are rare tumors with a dismal prognosis and a small number of systemic treatment options. STS may originate from mesenchymal stem cells (MSC); the latter have mainly been isolated from adult bone marrow (BM) as non-hematopoietic, self-renewing cells whose in vitro progeny comprises osteoblasts, chondroblasts, myocytes, and adipocytes. While in vitro expression profiles of MSC have been investigated extensively, the in vivo counterparts of MSC are still hypothetical. To target rare human cell BM populations including MSC, an exclusive antibody panel was developed. The target antigens include platelet-derived growth factor receptor-β (CD140b), HER-2/erbB2 (CD340), the recently described W8B2 antigen as well as several surface antigens identified by novel antibodies. To define the expression pattern of MSC-markers in STS, three STS cell lines were tested for expression of these antigens. In addition, snap-frozen primary STS sections were analyzed by immunohistochemistry using the same antibody panel. All cell lines revealed expression of selected markers including CD340, W8B2, and CD140b. Several MSC markers were restricted to a subpopulation of cells. In addition, leiomyosarcoma cells displayed a different expression pattern as compared to liposarcoma and Ewing’s sarcoma cells. Results of immunohistochemistry analysis of primary leiomyosarcoma tumor samples correlated strongly with expression patterns established by FACS analysis. However, important cytoarchitectural features regarding selected markers were revealed by immunohistochemistry: while primary leiomyosarcomas displayed uniform expression of W7C6, HEK3D6, CD10, and CD318, other markers such as CD34, W5C5, and 57D2 were expressed by tumor endothelia only. Moreover, a population of perivascular tumor cells was found to express the MSC-markers W4A5, W8B2, CD140b, W3D5, and W5C4. Novel MSC-markers are expressed by subpopulations in STS cell lines as well as in primary sarcoma tissue. Further studies on the functional significance of these phenotypical studies are underway and may help to identify novel specific targets recognizing the self-renewing STS-compartment.

Beschreibung: Abstract 4012 Poster Board III-948 Introduction Platelets are important contributors to several hallmarks of tumor pathophysiology including immune escape of disseminated malignant cells, metastasis, and neoangiogenesis. Following activation, platelets release their granule content, which contains a plethora of factors that may both inhibit and stimulate angiogenesis, immunosurveillance, plasmatic coagulation, or tumor growth. Targeted deletion of thrombospondin-1 and -2 from the platelet proteome leads to altered secretion of CXCL12 and matrix metalloproteinases (MMPs) in mice (Kopp HG, Hooper AT et al., J Clin Invest 2006), and platelets derived from 25 patients with lymphoma, colorectal and ovarian cancer displayed a diminished tsp-1/VEGF-ratio (Gonzalez FJ, Rueda A et al., Int J Biol Markers, 2004). We therefore set out to analyze a carefully selected patient cohort for in vivo platelet activation and platelet contents in order to define phenotypic changes in the setting of disseminated malignancy. Patients and methods Platelet activation in percent of P-selectin positive platelets and platelet contents (i.e. absolute platelet count-corrected plasma/serum levels of VEGF-A, CXCL12 [SDF-1], CXCL4 [pf4], and thrombospondin-1) were analyzed. Patients were eligible after written informed consent if they had a first diagnosis of metastatic malignancy, were not taking medication on a regular basis, and had not taken any medication during the last 14 days before venipuncture. Healthy age- and sex-matched subjects were used as controls. Results (mean ± SEM) Tumor patients had increased platelet counts (301,558 ± 17,489/μl vs. 234,111 ± 5,946/μl) and slightly lower hematocrits. In addition, cancer patients displayed significantly elevated percentages of activated platelets as measured by CD62P expression (1.14 ± 0.20% vs. 0.24 ± 0.03%). In order to obtain absolute platelet contents per 100 million platelets, we took tumor-associated thrombocytosis and anemia in consideration and calculated as follows: ([serum VEGF/CXCL12/TSP1/CXCL4 – plasma VEGF/CXCL12/TSP1/CXCL4] * [1-hematocrit] ÷ platelets per ml whole blood) * 100×106. The results showed highly significant changes, including increased contents of VEGF (143.24 ± 15.87 pg vs. 63.02 ± 6.28 pg; p 〈 0.001) and decreased amounts of thrombospondin-1 (2,925.13 ± 217.78 ng vs. 3,764.34 ± 184.64 ng; p = 0.005), CXCL4 (1,547.60 ± 44.54 ng vs. 1,132.32 ± 55.62 ng, p

Beschreibung: Waterbodies in the arctic permafrost zone are considered a major source of the greenhouse gas methane (CH4). Spatial extrapolation of these CH4 fluxes to a region or the circum-Arctic, however, are still associated with large uncertainties. Here, we address this issue by using a combination of airborne CH 4 flux measurements and waterbody mapping based on TerraSAR-X and Sentinel-1 data across two study areas (1000 km2) in the Mackenzie Delta, Canada. Our results indicate that permafrost waterbodies, even if they seem to be strong emitters on an individual basis, do not necessarily translate into significant CH 4 emission hot spots on a regional scale. Our results show inconsistent patterns in the correlations between waterbody types and the CH 4 flux in the two study areas and across different spatial resolutions. Technical advances enabling the determination of the CH4 flux of individual waterbodies across a region provide a prospective direction to improve our understanding.

Beschreibung: The goal of this study is to scale aircraft measured fluxes of sensible and latent heat to the North Slope of Alaska and develop high resolution flux maps. For this purpose we analyzed an eddy-covariance data set obtained by the research aircraft POLAR 5 as part of the AIRMETH-2012 campaign, and investigated the spatial patterning of energy fluxes. Environmental response functions between flux observations and corresponding biophysical and meteorological drivers were estimated using a combination of time-frequency decomposition, dispersion modeling and machine learning. The extracted relationships are then used to scale observational data across heterogeneous Arctic landscapes, thus improving the spatial coverage and representativeness of the energy fluxes. Maps of projected energy fluxes are used to asses energy partitioning in northern ecosystems and to determine dominant energy exchange processes of permafrost area.