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@article{faucris.270571625,
abstract = {In this work, we analyzed the reliability of alginate-gelatin microcapsules as artificial tumor model. These tumor-like scaffolds are characterized by their composition and stiffness (∼25 kPa), and their capability to restrict -but not hinder- cell migration, proliferation and release from confinement. Hydrogel-based microcapsules were initially utilized to detect differences in mechano-sensitivity between MCF7 and MDA-MB-231 breast cancer cells, and the endothelial cell line EA.hy926. Additionally, we used RNA-seq and transcriptomic methods to determine how the culture strategy (i.e. 2D v/s 3D) may pre-set the expression of genes involved in multidrug resistance, being then validated by performing cytotoxicological tests and assays of cell morphology. Our results show that both breast cancer cells can generate elongated multicellular spheroids inside the microcapsules, prior being released (mimicking intravasation stages), a behavior which was not observed in endothelial cells. Further, we demonstrate that cells isolated from 3D scaffolds show resistance to cisplatin, a process which seems to be strongly influenced by mechanical stress, instead of hypoxia. We finally discuss the role played by aneuploidy in malignancy and resistance to anticancer drugs, based on the increased number of polynucleated cells found within these microcapsules. Overall, our outcomes demonstrate that alginate-gelatin microcapsules represent a simple, yet very accurate tumor-like model, enabling us to mimic the most relevant malignant hints described in vivo, suggesting that confinement and mechanical stress need to be considered when studying pathogenicity and drug resistance of cancer cells in vitro. STATEMENT OF SIGNIFICANCE: In this work, we analyzed the reliability of alginate-gelatin microcapsules as an artificial tumor model. These scaffolds are characterized by their composition, elastic properties, and their ability to restrict cell migration, proliferation, and release from confinement. Our results demonstrate four novel outcomes: (i) studying cell migration and proliferation in 3D enabled discrimination between malignant and non-pathogenic cells, (ii) studying the cell morphology of cancer aggregates entrapped in alginate-gelatin microcapsules enabled determination of malignancy degree in vitro, (iii) determination that confinement and mechanical stress, instead of hypoxia, are required to generate clones resistant to anticancer drugs (i.e. cisplatin), and (iv) evidence that resistance to anticancer drugs could be due to the presence of polynucleated cells localized inside polymer-based artificial tumors.},
author = {Ertekin, Özlem and Monavari, Mahshid and Krüger, René and Fuentes Chandia, Miguel Angel and Parma, Beatrice and Letort, Gaelle and Tripal, Philipp and Boccaccini, Aldo R. and Boßerhoff, Anja Katrin and Ceppi, Paolo and Kappelmann-Fenzl, Melanie and Leal-Egaña, Aldo},
doi = {10.1016/j.actbio.2022.02.010},
faupublication = {yes},
journal = {Acta Biomaterialia},
peerreviewed = {Yes},
title = {{3D} hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance.},
year = {2022}
}
@inproceedings{faucris.238365243,
abstract = {We introduce a software framework that
assembles 3D animations of imaging data
using a textual description with a syntax
based on natural English language. In
contrast to the established key frame
based approach, smooth and complex
motion sequences are intuitively
implemented by concatenating multiple
instructions. [1] The syntax is extensible
and we demonstrate its integration into
existing 3D visualization software. The
user typically stores different rendering
settings and scene transformations in a
number of key frames along a timeline,
and the rendering engine creates a
smooth animation by interpolating
between them. Key frames save the
spatial transformation of an object as a
state, e.g. three angles for a rotation, and
not as a transition. This at least 4 key
frames are required to define a 360-
degree rotation with constant speed
unambiguously. Even more are required if the motion is non-linear, which is essential for achieving
smooth and pleasant motions. Software packages therefore typically provide a shortcut to insert key
frames for rotations around common axes. More complex motions such as combined rotations around
multiple axes, however, are difficult to achieve.
The syntax based on natural English language maximizes experience and provides easy access for
users of distinct fields. Each instruction is an English sentence. Complex motion sequences are
implemented by combining multiple instructions which are applied in the order they appear in the text.
The syntax comprises phrases for standard non-linear accelerations, resulting in smooth and natural
animations. Self-defined macro functions can be used to define motion and other parameters as
functions over time. We provide 3DScript as a Fiji/ImageJ plugin including an hardware-accelerated 3D
renderer and a dedicated editor featuring auto-completion and recording. Although tailored to the
included rendering engine, both the syntax and our animation framework can be easily adapted by other
rendering software.
100 %ID/g). Despite the unfavorable biodistribution, [(18)F]23 was successfully used for imaging of Y1R positive MCF-7 tumors in nude mice. Therefore, we suggest [(18)F]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y1R-dependent enrichment in mammary carcinom},
author = {Keller, Max and Maschauer, Simone and Brennauer, Albert and Tripal, Philipp and Koglin, Norman and Dittrich, Ralf and Bernhardt, Guenther and Kuwert, Torsten and Wester, Hans-Juergen and Buschauer, Armin and Prante, Olaf},
doi = {10.1021/acsmedchemlett.6b00467},
faupublication = {yes},
journal = {ACS Medicinal Chemistry Letters},
note = {EVALuna2:13870},
pages = {304-309},
peerreviewed = {Yes},
title = {{Prototypic} (18){F}-{Labeled} {Argininamide}-{Type} {Neuropeptide} {Y} {Y1R} {Antagonists} as {Tracers} for {PET} {Imaging} of {Mammary} {Carcinoma}},
volume = {8},
year = {2017}
}
@inproceedings{faucris.228171022,
address = {PHILADELPHIA},
author = {Britzen-Laurent, Nathalie and Guo, Wei and Langer, Victoria and Khoziainova, Svetlana and Weisenburger, Thomas and Winkler, Thomas and Straube, Julia and Waldner, Maximilian and Becker, Christoph and Naschberger, Elisabeth and Skottke, Lisa and Tripal, Philipp and Grivennikov, Sergei and Stürzl, Michael},
booktitle = {CANCER RESEARCH},
date = {2019-03-29/2019-04-03},
doi = {10.1158/1538-7445.SABCS18-5162},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-22},
peerreviewed = {unknown},
publisher = {AMER ASSOC CANCER RESEARCH},
title = {{Role} of {IFN}-gamma-activation of distinct tumor and stromal cell populations in colorectal carcinoma pathogenesis},
venue = {Atlanta, GA},
year = {2019}
}
@article{faucris.210667869,
abstract = {Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro-DLCs is proposed based on an N-alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium-based DLCs. Since ROS are overproduced in cancer, the high-efficiency cancer-cell-specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro-DLCs in vitro and in vivo. We prepared a conjugate of another pro-DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate.},
author = {Reshetnikov, Viktor and Daum, Steffen and Janko, Christina and Karawacka, Weronika and Tietze, Rainer and Alexiou, Christoph and Paryzhak, Solomiya and Dumych, Tetiana and Bilyy, Rostyslav and Tripal, Philipp and Schmid, Benjamin and Palmisano, Ralf and Mokhir, Andriy},
doi = {10.1002/anie.201805955},
faupublication = {yes},
journal = {Angewandte Chemie International Edition},
note = {EVALuna2:35451},
pages = {11943-11946},
peerreviewed = {Yes},
title = {{ROS}-{Responsive} {N}-{Alkylaminoferrocenes} for {Cancer}-{Cell}-{Specific} {Targeting} of {Mitochondria}},
volume = {57},
year = {2018}
}
@article{faucris.262159024,
abstract = {Recently, FRET probes for acid sphingomyelinase (ASM) have enabled the observation of enzyme activity in intact cells for the first time. Here we present an ASM FRET probe specifically optimized for 2-photon excitation. To facilitate probe characterization and comparison to the previous probe, we mixed the two intact probes with defined amounts of the probes' ceramide cleavage products and mounted them on lipid beads. Directly excited NBD FRET acceptor fluorescene proved to be a useful means of reference and showed that the new probe is brighter, albeit only moderately, than the previous one. The new probe was then used to detect inhibition by various ASM inhibitors microscopically for the first time. Also in cells, directly excited acceptor fluorescence proved to be a useful parameter in addition to FRET to visualize inhibition of ASM.},
author = {Mohamed, Zain H. and Rhein, Cosima and Schmid, Benjamin and Tripal, Philipp and Kornhuber, Johannes and Arenz, Christoph},
doi = {10.1016/j.bmc.2021.116303},
faupublication = {yes},
journal = {Bioorganic & medicinal chemistry},
keywords = {Antidepressants; Enzyme inhibitors; FRET probes; Förster resonance energy transfer (FRET); Sphingolipids; Two-photon microscopy},
note = {CRIS-Team Scopus Importer:2021-07-30},
peerreviewed = {Yes},
title = {{Synthesis} and characterization of a new two photon excitable acid sphingomyelinase {FRET} probe},
volume = {44},
year = {2021}
}
@article{faucris.242009111,
abstract = {Major depression is a severe mood disorder with a lifetime prevalence of more than 10%. The pharmacokinetic hypothesis claims that a slow accumulation of antidepressant drugs by acid trapping mainly into lysosomes is responsible for the therapeutic latency and that a lysosomal target mediates the antidepressant effects. The lysosomal lipid metabolizing enzyme acid sphingomyelinase (ASM) cleaves sphingomyelin into ceramide and phosphorylcholine. In a pilot study, the activity of this enzyme was increased in peripheral blood cells of patients with major depressive disorder (MDD), making the ASM an interesting molecular target of antidepressant drugs. Indeed, several antidepressant drugs functionally inhibit ASM. The ASM/ceramide pathway might be a missing link unifying independent findings in neurobiology and the treatment of MDD such as therapeutic latency, oxidative stress, immune activation and increased risk of cardiovascular disease. © 2009 Springer-Verlag.},
author = {Kornhuber, Johannes and Reichel, Martin and Tripal, Philipp and Groemer, Teja W. and Henkel, Andreas W. and Mühle, Christiane and Gulbins, Erich},
doi = {10.1007/s00406-009-0061-x},
faupublication = {yes},
journal = {European archives of psychiatry and clinical neuroscience},
keywords = {Acid sphingomyelinase; Amitriptyline; Ceramide; Fluoxetine; Lysosomes; Major depressive disorder; Neuroplasticity hypothesis; Pharmacokinetic hypothesis; Sphingolipids},
note = {Created from Fastlane, Scopus look-up},
pages = {S199-S204},
peerreviewed = {Yes},
title = {{The} role of ceramide in major depressive disorder},
volume = {259},
year = {2009}
}
@article{faucris.255355340,
abstract = {(1) Background: Despite progress in surgery and radio-chemotherapy of glioblastoma (GB), the prognosis remains very poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Enhancing oxidative phosphorylation-known as the anti-Warburg effect-with cyclic AMP activators has been demonstrated to drive GB cells from proliferation to differentiation thereby reducing tumor growth in a cell culture approach. Here we re-evaluate this treatment in a more clinically relevant model. (2) Methods: The effect of treatment with dibutyryl cyclic AMP (dbcAMP, 1 mM) and the cAMP activator forskolin (50µM) was assessed in a GB cell line (U87GFP+, 104 cells) co-cultured with mouse organotypic brain slices providing architecture and biochemical properties of normal brain tissue. Cell viability was determined by propidium-iodide, and gross metabolic effects were excluded in the extracellular medium. Tumor growth was quantified in terms of area, volume, and invasion at the start of culture, 48 h, 7 days, and 14 days after treatment. (3) Results: The tumor area was significantly reduced following dbcAMP or forskolin treatment (F2,249 = 5.968, p = 0.0029). 3D volumetric quantification utilizing two-photon fluorescence microscopy revealed that the treated tumors maintained a spheric shape while the untreated controls exhibited the GB typical invasive growth pattern. (4) Conclusions: Our data demonstrate that treatment with a cAMP analog/activator reduces GB growth and invasion.},
author = {Wartchow, Krista Mineia and Schmid, Benjamin and Tripal, Philipp and Stadlbauer, Andreas and Buchfelder, Michael and Goncalves, Carlos-Alberto and Kleindienst, Andrea},
doi = {10.3390/cells10030556},
faupublication = {yes},
journal = {Cells},
keywords = {2-photon-microscopy; glioblastoma; oxidative phosphorylation; treatment; Warburg effect},
note = {CRIS-Team Scopus Importer:2021-04-16},
peerreviewed = {Yes},
title = {{Treatment} with {Cyclic} {AMP} {Activators} {Reduces} {Glioblastoma} {Growth} and {Invasion} as {Assessed} by {Two}-{Photon} {Microscopy}},
volume = {10},
year = {2021}
}
@article{faucris.228588750,
abstract = {Nonclassical crystallization typically yields materials with pronounced roughness and porosity as it is driven by nanoparticle self-organization. Here, we demonstrate that bio-inspired nonclassical mineralization via magnesium-doped polymer-induced liquid precursors (PILP) can yield ultra-smooth and space-filling CaCO3 films featuring an unprecedented low roughness of 0.285 nm.},
author = {Harris, Joseph and Mey, Ingo P. and Böhm, Corinna and Trinh, Huyen and Leupold, Simon and Prinz, Carsten and Tripal, Philipp and Palmisano, Ralf and Wolf, Stephan},
doi = {10.1039/c9nh00175a},
faupublication = {yes},
journal = {Nanoscale Horizons},
note = {CRIS-Team WoS Importer:2019-11-01},
pages = {1388-1393},
peerreviewed = {Yes},
title = {{Ultra}-smooth and space-filling mineral films generated via particle accretion processes},
volume = {4},
year = {2019}
}
@article{faucris.229231771,
abstract = {Guanylate-binding proteins (GBPs) are the most abundant cellular proteins expressed in response to interferon-γ (IFN-γ), with seven highly homologous members in humans, termed HuGBP-1 to HuGBP-7. To date, differential features that may indicate differential functions of these proteins have not been described. Here, we investigated the expression and subcellular localization of the different HuGBPs in endothelial cells (EC). IFN-γ, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced the expression of HuGBP-1, HuGBP-2, and HuGBP-3 at similar high levels. In contrast, expression of HuGBP-4 and HuGBP-5 was robustly induced only by IFN-γ and not by TNF-α and IL-1β. Expression of HuGBP-6 and HuGBP-7 was not detected in EC under the various conditions examined. Investigating subcellular localization of the EC-expressed HuGBPs, HuGBP-1, HuGBP-3, and HuGBP-5 were exclusively detected in the cytoplasm, whereas HuGBP-2 and HuGBP-4 displayed a nucleocytoplasmic distribution. Treatment of the cells with IFN-γ and aluminum fluoride caused rapid enrichment of HuGBP-1 and HuGBP-2 in the Golgi apparatus, as demonstrated by time-lapse microscopy and fluorescence analyses of GFP-tagged HuGBPs. HuGBP-3 and HuGBP-4 were never detected in the Golgi apparatus, whereas HuGBP-5 was constitutively enriched in this cytosolic compartment, irrespective of stimulation. These results assign a characteristic pattern of expression and subcellular localization to each of the HuGBPs, indicating for the first time that these proteins may have different cellular functions. © Mary Ann Liebert, Inc.},
author = {Tripal, Philipp and Bauer, Michael and Naschberger, Elisabeth and Mörtinger, Thomas and Hohenadl, Christine and Cornali, Emmanuelle and Thurau, Mathias and Stürzl, Michael},
doi = {10.1089/jir.2007.0086},
faupublication = {yes},
journal = {Journal of Interferon and Cytokine Research},
note = {Created from Fastlane, Scopus look-up},
pages = {44-52},
peerreviewed = {Yes},
title = {{Unique} features of different members of the human guanylate-binding protein family},
volume = {27},
year = {2007}
}