Zielsetzung Die metronomische Chemotherapie (MCT) wird in der Onkologie aufgrund des günstigen therapeutischen Index zunehmend verwendet. Beim metastasierten Mammakarzinom (MBC) ist die MCT noch nicht ausreichend erprobt. Diese unizentrische, retrospektive Kohortenstudie sollte die Effektivität und Toxizität der MCT bei MBC untersuchen.

Zielsetzung Eine Hyperaktivierung des Phosphatidylinositol-3-Kinase (PI3K)-Signalweges steht im Zusammenhang mit Chemotherapieresistenz und einer ungünstigen Prognose bei Hormonrezeptor (HR)-positivem, HER2-negativem Mammakarzinom. Eine Hemmung des PI3K-Signalweges könnte die Resistenzbildung gegenüber zytotoxischen Medikamenten verhindern. Ziel dieser Arbeit war es, die antitumorale Aktivität der Kombination von niedrig dosiertem Vinorelbin (VRL) und Alpelisib, einem α-selektiven PI3K-Inhibitor und Degrader, in Mammakarzinomzellen zu untersuchen.

Zielsetzung Frailty ist ein häufig unterdiagnostiziertes multidimensionales Syndrom, das mit verminderten Leistungsreserven und einer erhöhten Anfälligkeit gegenüber Stressoren einhergeht. Zur Identifizierung von Patientinnen mit einem erhöhten Risiko für perioperative Komplikationen wurden Screening-Instrumente zur globalen Gesundheitsbeurteilung bei Ovarialkarzinom (OK)-Patientinnen untersucht.

The crystal structure and magnetic correlations in triangular antiferromagnet FeGa2S4 are studied by x-ray diffraction, magnetic susceptibility, neutron diffraction, and neutron inelastic scattering. We report significant mixing at the cation sites and disentangle magnetic properties dominated by major and minor magnetic sites. The magnetic short-range correlations at 0.77 angstrom(-1) correspond to the major sites and being static at base temperature they evolve into dynamic correlations around 30-50 K. The minor sites contribute to the magnetic peak at 0.6 angstrom(-1), which vanishes at 5.5 K. Our analytical studies of triangular lattice models with bilinear and biquadratic terms provide the ratios between exchanges for the proposed ordering vectors. The modeling of the inelastic neutron spectrum within linear spin-wave theory results in the set of exchange couplings J(1) = 1.7, J(2) = 0.9, J(3) = 0.8 meV for the bilinear Heisenberg Hamiltonian. However, not all features of the excitation spectrum are explained with this model.

Purpose In the treatment of both metastatic breast cancer (MBC) and platinum-resistant recurrent ovarian cancer (ROC), symptom control and maintenance of quality of life (QoL) play a crucial role. In the advanced stage of disease, metronomic chemotherapy (MCT) may be a favourable treatment option. The aim of this study is to assess the QoL of heavily pretreated patients with MBC and ROC treated with MCT.

Background In preliminary work we identified KDM5B and CBX5 as potential target structures of the humoral immune response in TNBC patients using phage display technique. Both KDM5B and CBX5 are known as gene-regulating proteins: while KDM5B acts as a histon lysine demethylase, CBX5 regulates gene expression mainly through chromatin modification. In this project we evaluated the KDM5B and CBX5 expression and its prognostic impact on mRNA and protein level in breast cancer.

Einleitung Die NAKO Gesundheitsstudie ist eine prospektive Langzeit-Bevölkerungsstudie, welche die ätiologischen Pfade von Lebensstil-, Umwelt- und genetische Faktoren zu chronischen Krankheiten (wie z.B. des Herz-Kreislaufsystems, der Lunge, Diabetes, Krebs) erforscht. Zu diesem Zweck wurden über 205.000 Männer und Frauen im Alter von 20 bis 69 Jahren an 18 Studienstandorten in Deutschland untersucht.

During laser keyhole welding of metal sheets, a process regime has been observed where no stable welding process sets in. Instead, material is ejected at the keyhole bottom, leading to the formation of a cutting kerf. The forces driving the melt ejection originate from the laser material interaction itself opposite to conventional fusion cutting, where an assist gas has to be used to enforce the melt ejection. As there is no need for a local application of auxiliary materials or gases, this holds the potential for a remote fusion cutting process. So far, only initial research exists concerning its occurrence and the underlying physical mechanisms are barely understood. Therefore, we use high-speed imaging of the cutting front and the melt ejection to generate insights into the melt dynamics. An evaluation approach is presented which incorporates image processing to enable the automated processing of large datasets, allowing a quantification of the observed effects and the evaluation of large-scaled studies of the melt behaviour for different parameters. The presented methodology enables the investigation of the mechanisms leading up to stable remote fusion cutting.

Triple negative breast cancer (TNBC) presents with an aggressive clinical phenotype lacking expression of conventional drug targets. Overall survival in early- and advanced-stage disease is poor. TNBC-MERIT is a phase I trial (NCT02316457) assessing the feasibility, safety and immunogenicity of a liposome-formulated intravenous RNA vaccine encoding different tumor antigen categories in TNBC patients after surgery and (neo-)adjuvant chemotherapy. Patients in two arms of this trial received a personalized set of pre-manufactured non-mutated shared tumor-associated antigens with or without universal T helper epitopes. In a third arm, patients were vaccinated with IVAC_M_uID, an on-demand manufactured Individualized NeoAntigen Specific Immunotherapy (iNeST) encoding neoepitopes derived from up to 20 cancer mutations determined by NGS. This report provides a preliminary data analysis of immune responses in IVAC_M_uID-vaccinated patients as analyzed by IFNγ-ELISpot, multimer staining, TCR repertoire profiling and single cell TCR sequencing (data final mid-2020). Immunogenicity data was generated from all 14 IVAC_M_uID-treated patients. All analyzed patients had vaccine-induced CD4+ and/or CD8+ T-cell responses against 1 to 10 of the vaccine neoepitopes detected by IFNγ ELISpot, ex vivo or after in vitro stimulation. A substantial number of T-cell responses against individual neoepitopes were induced de novo and of high magnitude (up to 10.3% of peripheral CD8 T cells). One of the index patients characterized in more detail mounted CD4+ and/or CD8+ T-cell responses against 10 of 20 vaccine neoepitopes. The highly poly-epitopic TCR-clonotype diversified CD8+ T-cell response comprised in aggregate about 30% of total peripheral CD8+ T cells and was sustained at high levels for at least 6 months after the last vaccination. Vaccine-induced CD8+ T cells were of effector/memory, PD1+ phenotype, with a high fraction IFNγ/TNFα/Mip-1a&b triple-positive. This preliminary data suggests that the iNeST IVAC_M_uID is highly efficient in inducing strong poly-epitopic T-cell responses in patients with TNBC in the post-(neo) adjuvant setting.

The current trend of mass customization pushes conventional production techniques to their limits. In the case of forming technology, limitations in terms of adaptability and flexibility emerge, while additive manufacturing lacks in the manufacturing of large, geometrically simple components. Combining both processes has potential to use the strengths of each process and thus realize time and cost efficient mass customization. As the interactions between the processes have not been fully investigated yet, in this work a distinct modelling approach in LS-DYNA is used to examine the influence of the additively manufactured elements on the formability. Namely, varying geometric properties and number of pins created with additive manufacturing are in the focus of this research. The used material is the alloy Ti-6Al-4V, which requires processing at elevated temperatures due to its low formability at room temperature. The results show a clear influence of the additively manufactured elements on the formability.

Background A high level of tumor-infiltrating plasma cells in TNBC may be an indication for immunogenic potential, which could be used as a valuable potential therapeutic tool. To identify potential target structures of the humoral immune response, we analyzed the antibody signatures in plasma from TNBC patients with a high level of tumor infiltrating plasma cells compared to plasma samples of TNBC patients with low plasma cell infiltration in the primary tumor.