Honeybees Learn Landscape Features during Exploratory Orientation Flights

Degen J, Kirbach A, Reiter L, et al. Honeybees Learn Landscape Features during Exploratory Orientation Flights. Current Biology. 2016;26(20):2800-2804

Long-lived tumor-associated macrophages in glioma.

Background: The tumor microenvironment plays a major tumor-supportive role in glioma. In particular, tumor-associated macrophages (TAMs), which can make up to one-third of the tumor mass, actively support tumor growth, invasion, and angiogenesis. Predominantly alternatively activated (M2-polarized) TAMs are found in late-stage glioma in both human and mouse tumors, as well as in relapse samples from patients. However, whether tumor-educated M2 TAMs can actively contribute to the emergence and growth of relapse is currently debated. Methods: To investigate whether tumor-educated stromal cells remaining in the brain after surgical removal of the primary tumor can be long-lived and retain their tumor-supporting function, we developed a transplantation mouse model and performed lineage-tracing. Results: We discovered that macrophages can survive transplantation and stay present in the tumor much longer than previously suggested, while sustaining an M2-polarized protumorigenic phenotype. Transplanted tumors showed a more aggressive growth and faster polarization of the TAMs toward an M2 phenotype compared with primary tumors, a process dependent on the presence of few cotransplanted macrophages. Conclusions: Overall, we propose a new way for tumor-educated TAMs to contribute to glioma aggressiveness by long survival and stable protumorigenic features. These properties could have a relapse-supporting effect.status: Published onlin

ATTRACT Arterial Flow as Attractor for Endothelial Cell Migration

status: publishe

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences.status: publishe

4. Editorial Support Group:

STOYANOVA, Daniela (English version

Structure-activity relationship of dihydroxy-4-methylcoumarins as powerful antioxidants: Correlation between experimental & theoretical data and synergistic effect

The chain-breaking antioxidant activities of eight coumarins [7-hydroxy-4-methylcoumarin (1), 5,7-dihydroxy-4-methylcoumarin (2), 6,7-dihydroxy-4-methylcoumarin (3), 6,7-dihydroxycoumarin (4), 7,8-dihydroxy-4-methylcoumarin (5), ethyl 2-(7,8-dihydroxy-4-methylcoumar-3-yl)-acetate (6), 7,8-diacetoxy-4-methylcoumarin (7) and ethyl 2-(7,8-diacetoxy-4-methylcoumar-3-yl)-acetate (8)] during bulk lipid autoxidation at 37 degrees C and 80 degrees C in concentrations of 0.01-1.0 mM and their radical scavenging activities at 25 degrees C using TLC-DPPH test have been studied and compared. It has been found that the o-dihydroxycoumarins 3-6 demonstrated excellent activity as antioxidants and radical scavengers, much better than the m-dihydroxy analogue 2 and the monohydroxycoumarin 1. The substitution at the C-3 position did not have any effect either on the chain-breaking antioxidant activity or on the radical scavenging activity of the 7,8-dihydroxy- and 7,8-diacetoxy-4-methylcoumarins 6 and 8. The comparison with DL-alpha-tocopherol (TOH), caffeic acid (CA) and p-coumaric acid (p-CumA) showed that antioxidant efficiency decreases in the following sequence: TOH > CA > 3 > 4 > 6 > 5 > 2 > 1 = 7 = 8 = p-CumA. Theoretical calculations and the "Lipinski's Rule of Five" were used for explaining the structure activity relationships and pharmacokinetic behavior. A higher TGSO oxidation stability was observed in the presence of equimolar (1:1) binary mixtures of coumarins with TOH (1 + TOH, 3 + TOH and 5 + TOH). However, the synergism (14%) was observed only for the binary mixture of 5 + TOH. (C) 2010 Elsevier Masson SAS. All rights reserved

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences

Abstracts Of The Proceedings And The Posters From The Third Scientific Session Of The Medical College Of Varna

October 2-3, 201