Die klinische Bedeutung des carcinoembryonalen Antigens (CEA) für Patienten mit hereditärem nicht-polypösem kolorektalem Karzinom (HNPCC)

Das carcinoembryonale Antigen (CEA) ist insbesondere als Tumormarker für das kolorektale Karzinom anerkannt. Auf die hereditäre Form "HNPCC" lässt sich seine Bedeutung jedoch nicht äquivalent übertragen

Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: Current status and future perspectives

Abstract Background Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. Methods Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion. Results Monotherapy with anti–PD-1/PD-L1 antibodies, including pembrolizumab, nivolumab, avelumab, durvalumab, and atezolizumab, has shown interesting objective response rates (ORRs; 7–26%) across varying GC/GEJC populations, with ORRs potentially higher in PD-L1 + vs PD-L1 − tumors. Safety profiles compare favorably with chemotherapy, with grade ≥3 treatment-related adverse events occurring in 5–17%. Based on a large phase 2 study, pembrolizumab was approved in the United States for third-line treatment of patients with PD-L1 + GC/GEJC. In a phase 3 trial, third-line or later nivolumab increased overall survival vs placebo in an Asian population, leading to regulatory approval in Japan, although other completed phase 3 trials did not show superiority for pembrolizumab or avelumab monotherapy vs chemotherapy. Other trials in advanced GC/GEJC are assessing various anti–PD-1/PD-L1–based strategies, including administration in first-line and later-line settings and as combination (with chemotherapy or agents targeting other immune checkpoint proteins, eg, CTLA-4, LAG-3, and IDO) or switch-maintenance regimens. Conclusions Anti–PD-1/PD-L1 antibodies have shown encouraging clinical activity in advanced GC/GEJC. Results from ongoing phase 3 trials are needed to further evaluate the potential roles of these agents within the continuum of care

MOL#8268 1 Title Page. The natural mutation encoding a C-terminus truncated 5-HT 2B receptor is a gain of proliferative functions

Number of tables, 1 Number of references, 31 Number of words in the abstract, 230 Number of words in the Introduction, 744 Number of words in the Discussion. 1172 List of non-standard abbreviations receptor was identified in one patient diagnosed with pulmonary hypertension after intake of the anorexigen dexfenfluramine. Although reported to generate a lack of function, this C-terminus truncated 5-HT 2B receptor should somehow affect transduction pathways relevant to pulmonary hypertension. In our study, we investigated putative modifications in transduction of the R393X mutated 5-HT 2B receptor. In stably transfected cells, we confirmed the loss of IP 3 stimulation due to the G αq uncoupling, despite conserved ligand affinity between the normal and mutated receptors. We also observed a partial loss of nitric oxide synthase stimulation. However, the truncated R393X receptor presented (i) a strong gain of efficacy in cell proliferation as assessed by mitogen-activated protein kinase activity and thymidine incorporation, (ii) a preferential coupling to G α13 as shown by blocking antiserum, and (iii) an apparent lack of internalization upon agonist stimulation as observed by confocal microscopy. This work demonstrates that, in the 5-HT 2B receptor, the C-terminus including the palmitoylation and phosphorylation sites is absolutely required for proper transduction and internalization. For the first time, we show that the lack of C-terminus can generate a switch of coupling to G α13 , a reduced NO synthase activation and an increase in cell proliferation. All these modifications are relevant in pathophysiological vasoconstriction. MOL#8268 4 Introduction

Comparative proteome analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and organ donors

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Symmetry methods for turbulence modeling

The given thesis is based on the turbulence theory based on Lie group methods, which has been developed in the last couple of years. With this theory at hand it is possible to derive classical semi-empirical approaches, as for example the law of the wall, from "first principles". Here three different flow cases, which are the turbulent diffusion, the zero-pressure gradient turbulent boundary layer flow and the fully developed turbulent rotating pipe flow have been investigated. Using symmetry methods linear and non-linear eddy viscosity models as well as Reynolds stress models have been analyzed. Thereby it has been checked if the model equations have the same symmetry properties as the two-point correlation equations and if they are able to describe the turbulent scaling laws which have been derived for the given flow cases. Based on these investigations conditions for the model constants and the structure of the model equations have been derived