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Einfluss von PD-(L)1-Checkpoint-Inhibitoren auf die Lebensqualität von Patienten mit fortgeschrittenem oder metastasiertem Urothelkarzinom im Vergleich zur Chemotherapie
Get PDFWir führten eine Analyse der Lebensqualität von Patienten mit metastasierten Urothelkarzinomen durch, die systemisch entweder mit einer zytotoxischen Chemotherapie oder mit PD-(L)1-Checkpoint-Inhibitoren im Rahmen einer Immuntherapie behandelt wurden.
In der Chemotherapie-Gruppe wurde beim Großteil der Patienten eine Verschlechterung der Lebensqualität (operationalisiert als der Wert des ermittelten „Global Health Status“ des EORTC-QLQ-C30-Fragebogens) beobachtet.
In der Immuntherapie-Gruppe (n=17) hingegen konnte der überwiegende Anteil der Patienten ihre Lebensqualität unter der Therapie erhalten oder sogar verbessern.
Die Auswertung des Parameters „FACT-BL Total Score“ des blasentumor-spezifischen FACT-BL-Fragebogens ergab im Hinblick auf die Lebensqualität nur moderate Abweichungen vom Baseline-Mittelwert, in der Dynamik der Daten jedoch vergleichbare Ergebnisse: in der Chemotherapie-Gruppe zeigte sich eine moderate Verschlechterung der Werte, in der Immuntherapie-Gruppe dagegen eine marginale Verbesserung.
Bei Patienten der Chemotherapie-Gruppe beobachteten wir im Verlauf der beiden Erhebungen zudem eine signifikante Verschlechterung des Parameters „Physical Functioning Score“ des EORTC-QLQ-C30, die mit der höheren Toxizität der Chemotherapie assoziiert werden kann.
Ein weiterer signifikanter Unterschied ergab sich beim Vergleich des Parameters „Emotional Functioning Score“ zwischen den Therapiegruppen zum Zeitpunkt der zweiten Erhebung. Die schlechteren Werte der Chemotherapie-Gruppe können zunächst erneut mit der höheren Toxizität und der damit verbundenen stärkeren körperlichen Beeinträchtigung der Patienten erklärt werden. Ein weiterer kausaler Faktor könnte in diesem Kontext darin bestehen, dass PD-(L)1-Checkpoint-Inhibitoren als neue, innovative Therapie-Optionen beim medizinischen Personal und den Patienten größere Hoffnungen und stärkere Zuversicht erwecken, und somit zu einer vergleichsweise geringeren emotionalen Belastung der Patienten beitragen
Therapeutic RIG-I activation enhances survival and induces sensitivity to immune checkpoint blockade therapy in preclinical models of AML
Get PDFDissection and proteome analysis to characterize the adult neural stem cell niche
Get PDFStem cell niches in the adult mammalian brain are decisively shaped by their microenvironment. In these niches, extracellular signals modulate stem cell quiescence, proliferation, migration, and differentiation. Conversely, the microenvironment in the remainder of the brain merely permits gliogenesis, restricts neuronal plasticity, and limits the neurogenic potential of neural precursors. Elucidating the mechanisms rendering neurogenic niches permissive for neurogenesis might foster the improvement of cell replacement therapies for neurological disorders involving neural cell loss. To better understand the molecular composition, the architecture, and the physical properties responsible for the neurogenic nature of the microenvironment in neural stem cell niches, this study pursued a characterization of the subependymal zone of the lateral ventricle (SEZ), which is the largest stem cell niche of the murine brain. To investigate the microenvironment of the SEZ, a bottom-up proteomic approach using mass spectrometry was employed. The analysis of the extracellular microenvironment of this region requires a precise dissection method with minimal tissue perturbation, applicable to unfixed tissue. For this purpose, a novel dissection method, termed Cryo-section Dissection (CSD), was developed. In the first step of the CSD protocol the cortex and the corpus callosum covering the lateral ventricles are removed from the unfixed murine brain. Then, after freezing the tissue on dry ice, the brain is sectioned coronally. Finally, the SEZ is manually isolated from each section using a pre-cooled scalpel. The SEZ as adult neural stem cell niche was compared to the non-neurogenic somatosensory cortex, the olfactory bulb as site of neuronal integration, and the structurally similar, but mostly non-neurogenic medial wall of the lateral ventricle, termed medial ependymal zone (MEZ). A library-matched single shot mass spectrometry analysis employing a label-free quantification algorithm was applied to generate the proteome data of the SEZ, the somatosensory cortex, the olfactory bulb, and the MEZ. This proteome data was used to investigate niche specific protein clusters and filtered for individual candidate proteins. Promising candidates were subjected to immunohistochemical staining. This analysis enabled the detection of the candidate proteins C1ql3, Kininogen 1, and S100a6 potentially involved in neurogenesis. Additionally, the influence of niche stiffness on neural stem cell physiology was investigated, and the extracellular neurogenesis regulator Transglutaminase 2 could be identified
Untersuchung zur Optimierung der automatisierten Isoflurannarkose für die Ferkelkastration mit den drei Narkosegeräten PigNap 4.0, PorcAnest 3000® und Anestacia®
Get PDFSince 01.01.2021, suckling piglets may no longer be castrated without anaesthesia in Germany. Previous studies showed castration using isoflurane anaesthesia in combination with a suitable analgesic, meet the requirements of the German Animal Welfare Act. It can be carried out independently by farmers and other qualified persons with an automated and certified isoflurane device. Therefore, the aim of the present field study was to implement the use of three different anaesthetic devices for surgical castration of male piglets under automated isoflurane anaesthesia on 15 conventional pig farms in southern Germany. In addition, the depth of anaesthesia based on defensive movements, the labour time required in contrast to anaesthetic-free castration, castration-related anaesthetic incidents and the piglet mortality rate as well as occupational safety were investigated. For this purpose, farrowing batches of 11574 piglets castrated under isoflurane anaesthesia (IA) were compared with the results of the 1568 piglets of anaesthetic-free farrowing batches (AF)
fMRT-Untersuchung über neurobiologische Korrelate bei Patienten mit phobischem Schwankschwindel und Angststörung
Get PDFInvestigating Lyman continuum escape fractions of high redshift galaxies during the era of reionization
Get PDFUntersuchung eines digitalen Registrierverfahrens der Kieferbewegung zur Herstellung von adjustierten Aufbissschienen
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Translating molecular concepts to the solid state
Get PDFCovalent organic frameworks are a novel class of crystalline and porous framework materials composed of light elements linked by covalent bonds between their building units. Their unique combination of properties, including permanent porosity, chemical and structural stability, light absorption, and versatility in structural design and composition, has led to an ever-expanding range of applications, including energy storage and conversion, heterogeneous (photo)catalysis, gas adsorption, and sensing. Even though COFs are solid-state materials, their organic composition promises unparalleled possibilities for modifications in chemical structure with similar versatility and precision as known from small organic molecular compounds. This comparability is inspiring for transferring additional classical molecular concepts to this class of solid-state materials.
In this thesis we transfer typical molecular concepts, such as the modification of organic functional groups as part of the chemical structure, stimuli-responsive dynamics and mobility, to covalent organic frameworks – as solid-state materials.
We present novel topochemical modification methods for post-synthetic linkage conversion of imine linkages to convert imine COFs into secondary amine-linked and nitrone-linked frameworks. These methods allow for a fine-tuning of materials properties, such as the stabilization of their chemical connectivity, reactivity for further functionalization, and pore channel polarity. To follow the conversion of bonds, properties, and structure, we employ a diverse set of analytical techniques, including FT-IR and solid-state NMR spectroscopy, gas and vapor sorption experiments and X-ray powder diffraction coupled with pair-distribution function analysis.
With the aim to study stimuli-responsive dynamics in COFs, we synthesize the first covalent organic framework with light-driven molecular motors embedded as building blocks in its chemical structure. The dynamics of the rotors in the material are probed by in situ spectroscopic techniques including Raman, FT-IR and UV-Vis spectroscopy. Although the presented materials fulfill important characteristics such as permanent porosity and thus, void space for motor rotation, motor isomerization could not be visualized by available analysis techniques, but allowed to gain insights into experimental and design challenges for transferring this property to solid-state materials. These findings allow to extend the design principles for the construction of next-generation dynamic COFs with stimuli-triggered response.
Finally, we study mobility by means of self-diffusion of acetonitrile in an imine-linked covalent organic framework by pulsed field gradient NMR experimentation, complemented by computational simulation methods, i.e. molecular dynamics simulations