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Current treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC) delays disease progression and improves survival, but resistance is inevitable. Additional therapies that prolong survival are needed. Androgen deprivation therapy (ADT) combined with next-generation hormonal agents, such as enzalutamide, is standard-of-care for men with mHSPC. Emerging evidence suggests potential synergism between enzalutamide and the PD-1 inhibitor pembrolizumab in prostate cancer. The phase III randomized, placebo-controlled, double-blind KEYNOTE-991 trial will investigate the efficacy and safety of pembrolizumab versus placebo in combination with enzalutamide when initiating ADT in participants with mHSPC naive to next-generation hormonal agents. Approximately 1232 patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks or placebo every 3 weeks, both with enzalutamide 160 mg once daily and ADT. Dual primary end points are overall survival and radiographic progression-free survival. Secondary end points include time to first subsequent therapy, time to symptomatic skeletal related event, objective response rate and safety and tolerability. Clinical Trial Registration: NCT04191096 ( ClinicalTrials.gov ).

Elektronische Reproduktion von: Das Riesen-Faulthier, Bradypus giganteus : abgebildet, beschrieben und mit den verwandten Geschlechtern verglichen / von Chr. Pander und E. D'Alton. - Bonn : Weber, 1821. - 3 [Bl.], 18 S. : Ill. - Standort: Universität Marburg, Universitätsbibliothek. - Signatur: 085 1 2022/00048. - Bemerkungen: Provenienz: Bünger, Christian Heinrich (1782-1842). Digitalisiert 2023

Elektronische Reproduktion von: Prima carotidi communiutrique corporis humani prospero cum eventu applicata ligatura, qua vita aegri servata et aneurysma eius late diffusum arteriae temporalis superficialis sinistrae totius, partisque arteriae frontalis et occipitalis plane est sanatum : quo libello viro perillustri Ferdinando Wurzer ... doctoratus in medicina impetrati semisaecularia gratulatur / Christian Heinrich Bünger. - Marburgi : Elwert, 1838. - 16 S. Hochschulschrift: Marburg, Univ., Diss.,1838. - Standort: Universität Marburg, Universitätsbibliothek. - Signatur: 085 1 2022/00071,21. - Bemerkungen: Provenienz: Bünger, Christian Heinrich (1782-1842). Digitalisiert 2023

Immunotherapies against high-risk neuroblastoma (NB), using the anti-GD2 antibody (Ab) dinutuximab beta (DB), significantly improved patient survival. Ab-dependent cellular cytotoxicity (ADCC) is one of the main mechanisms of action and it is primarily mediated by NK cells. To further improve antitumor efficacy, we investigated here a combinatorial immunotherapy with DB and the double immune checkpoint blockade of T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death ligand-1 (PD-L1). The effects of ADCC, mediated by DB against NB cells on NK-cell activity, and the expression of TIGIT and CD226 and their ligands CD112 and CD155, as well as of PD-1 and PD-L1 on NB and effector cells, were investigated using flow cytometry. ADCC was assessed with a calcein-AM-based cytotoxicity assay. The efficacy of a combinatorial immunotherapy with DB, given as a long-term treatment, and the double immune checkpoint blockade of TIGIT and PD-L1 was shown using a resistant murine model of NB, followed by an analysis of the tumor tissue. We detected both TIGIT ligands, CD112 and CD155, on all NB cell lines analyzed. Although ADCC by DB resulted in a strong activation of NK cells leading to an effective tumor cell lysis, a remarkable induction of PD-L1 expression on NB cells, and of TIGIT and PD-1 on effector cells, especially on NK cells, was observed. Additional anti-TIGIT or anti-PD-L1 treatments effectively inhibited tumor growth and improved survival of the mice treated with DB. The superior antitumor effects were observed in the “DB + double immune checkpoint blockade” group, showing an almost complete eradication of the tumors and the highest OS, even under resistant conditions. An analysis of tumor tissue revealed both TIGIT and TIGIT ligand expression on myeloid-derived suppressor cells (MDSCs), suggesting additional mechanisms of protumoral effects in NB. Our data show that the targeting of TIGIT and PD-L1 significantly improves the antitumor efficacy of anti-GD2 immunotherapy, with DB presenting a new effective combinatorial treatment strategy against high-risk tumors.

Jahresschrift für mitteldeutsche Vorgeschichte, Bd. 85 (2002): Jahresschrift für mitteldeutsche Vorgeschichte

Thrust collars relieve the gearbox housing of the axial force and tilting moments generated by helical gears. The different transfer path also reduces the vibration excitation of the housing due to meshing, which could lead to improved acoustics. This paper presents measurements of noise level reduction of an experimental gearbox. A gearbox dynamics simulation model is used to investigate the effects resulting from the inclusion of thrust collars.

Elektronische Reproduktion von: Die Skelete der Raubthiere : abgebildet und verglichen / von Chr. Pander und E. D'Alton. - Bonn : Weber, 1822. - 4 [Bl.], 15 S. : Ill. - Standort: Universität Marburg, Universitätsbibliothek. - Signatur: 085 1 2022/00050 Bemerkungen: Provenienz: Bünger, Christian Heinrich (1782-1842). Digitalisiert 2023

Elektronische Reproduktion von: Die Skelete der zahnlosen Thiere / abgebildet und verglichen von Chr. Pander und E. D'Alton. - Bonn : Weber, 1825. - 13 S. : Ill. - Standort: Universität Marburg, Universitätsbibliothek. - Signatur: 085 1 2022/00054. - Bemerkungen: Provenienz: Bünger, Christian Heinrich (1782-1842). Digitalisiert 2023