6 research outputs found

    Modified Poly(ε-caprolactone)s: An Efficient and Renewable Access via Thia-Michael Addition and Baeyer–Villiger Oxidation

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    The preparation of a novel class of ε-caprolactone (CL) monomers, modified at the β-position of the ester function, is described. The efficient thia-Michael addition to cyclohex-2-en-1-one and subsequent Baeyer–Villiger oxidation provided the regioselectively modified CL monomers. To enable a sustainable Baeyer–Villiger oxidation, several reaction procedures were investigated. In order to test a controlled ring-opening polymerization of the prepared monomers, the kinetics were studied and the monomer to initiator ratios were varied in order to prepare poly­(ε-caprolactone)­s with different molecular weights and different side groups

    Abstract 3967: ErbB2/HER2-specific natural killer cells for adoptive immunotherapy of glioblastoma.

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    Abstract In addition to primary natural killer (NK) cells, continuously growing cytotoxic cell lines such as NK-92 are being considered for adoptive cancer immunotherapy. High cytotoxicity of NK-92 has been shown against malignant cells of hematologic origin in preclinical studies, and general safety of infusion of NK-92 cells has been established in phase I clinical trials. To enhance their therapeutic utility, we genetically modified NK-92 cells to express chimeric antigen receptors (CAR) specific for different tumor-associated surface antigens including ErbB2 (HER2). Such CAR were composed of a tumor-specific scFv antibody fragment fused via hinge and transmembrane domains to intracellular signaling proteins such as CD3 zeta chain or a composite CD28-CD3 zeta fusion molecule. Glioblastoma multiforme (GBM) is the most common and severe intracranial malignant tumor in humans. Despite aggressive therapy, recurrence of GBM is very frequent, and the median survival of GBM patients is only 12 to 15 months. Since enhanced ErbB2 expression was found in up to 80% of GBM cases, adoptive ErbB2-targeted immunotherapy may represent a more efficient alternative to standard therapy. For development towards clinical applications, here we generated a lentiviral second generation CAR construct (5.28.z) specific for the ErbB2 antigen, and established GMP-compliant protocols for transduction and expansion of NK-92 cells. An ErbB2-specific single cell clone (NK-92/5.28.z) was isolated, which showed high and selective cytotoxicity towards different established ErbB2-expressing glioblastoma cells and tumor cells of various other origins in vitro, as well as specific tumor homing in murine in vivo models. Treatment with NK-92/5.28.z cells also resulted in marked inhibition of the growth of subcutaneous glioblastoma xenografts in NOD/SCID γc KO mice. Ongoing work now focuses on evaluating the feasibility and efficacy of intracranial application of NK-92/5.28.z cells in orthotopic xenograft models of ErbB2-positive glioblastoma cells as a basis for further development of these cells as an adoptive immunotherapy for glioblastoma patients. Citation Format: Concong Zhang, Kurt Schönfeld, Michael Burger, Sabrina Genßler, Christiane Sahm, Christian Brendel, Sonja Naundorf, Marcus Odendahl, Ulrike Köhl, Torsten Tonn, Manuel Grez, Joachim P. Steinbach, Winfried S. Wels. ErbB2/HER2-specific natural killer cells for adoptive immunotherapy of glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3967. doi:10.1158/1538-7445.AM2013-3967</jats:p

    Criterion 4: Maintenance, Conservation and Appropriate Enhancement of Biological Diversity in Forest Ecosystems

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    The maintenance, conservation, and appropriate enhancement of biodiversity remains an important goal for forest management in Europe. Biodiversity is generally considered valuable per se as well as being important for the adaptability and stability of forests. Forest management can support biodiversity through a range of practices – such as supporting natural regeneration and expansion, leaving part of the wood for decomposition, designating valuable habitats as protected areas or genetic conservation units, actively systematically protecting genetic resources of tree species, and suppressing invasive species

    Dominance and rarity in tree communities across the globe:Patterns, predictors and threats

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    Aim: Ecological and anthropogenic factors shift the abundances of dominant and rare tree species within local forest communities, thus affecting species composition and ecosystem functioning. To inform forest and conservation management it is important to understand the drivers of dominance and rarity in local tree communities. We answer the following research questions: (1) What are the patterns of dominance and rarity in tree communities? (2) Which ecological and anthropogenic factors predict these patterns? And (3) what is the extinction risk of locally dominant and rare tree species?. Location: Global. Time period: 1990–2017. Major taxa studied: Trees. Methods: We used 1.2 million forest plots and quantified local tree dominance as the relative plot basal area of the single most dominant species and local rarity as the percentage of species that contribute together to the least 10% of plot basal area. We mapped global community dominance and rarity using machine learning models and evaluated the ecological and anthropogenic predictors with linear models. Extinction risk, for example threatened status, of geographically widespread dominant and rare species was evaluated. Results: Community dominance and rarity show contrasting latitudinal trends, with boreal forests having high levels of dominance and tropical forests having high levels of rarity. Increasing annual precipitation reduces community dominance, probably because precipitation is related to an increase in tree density and richness. Additionally, stand age is positively related to community dominance, due to stem diameter increase of the most dominant species. Surprisingly, we find that locally dominant and rare species, which are geographically widespread in our data, have an equally high rate of elevated extinction due to declining populations through large-scale land degradation. Main conclusions: By linking patterns and predictors of community dominance and rarity to extinction risk, our results suggest that also widespread species should be considered in large-scale management and conservation practices.</p
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