Rekrutierung myeloischer Zellen durch EGFR-gerichtete Antikörper

Mit Cetuximab, Necitumumab und Panitumumab sind drei gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) gerichtete Antikörper für die Behandlung epithelialer Karzinome zugelassen. Während Cetuximab und Necitumumab zum Immunglobulin G (IgG)-Isotyp 1 gehören, ist Panitumumab ein IgG2-Antikörper. Nur von IgG1-Antikörpern ist man der Auffassung, dass diese in der Lage seien, mittels spezieller Bindungsstellen die Zerstörung der Tumorzellen vermitteln zu können. Zu diesen indirekten Effekten gehören die Aktivierung des Komplementsystems (komplementvermittelte Zytotoxizität) und die Rekrutierung von Immunzellen (antikörperabhängige zellvermittelte Zytotoxizität). Der IgG2-Isotyp wird hingegen für immunologisch inert gehalten und präferenziell dann ausgewählt, wenn keine der oben erwähnten Effekte gewünscht sind. Entgegen den Annahmen zeigte Panitumumab in Vorstudien jedoch eine starke Aktivierung myeloischer Zellen und erwies sich in vergleichenden klinischen Studien als gleichwertig effektiv wie Cetuximab. IgG1-, aber auch IgG2-Antikörper induzierten effektive Zytotoxizitäten gegenüber Tumorzellen in Anwesenheit myeloischer Effektorzellen wie M1-Makrophagen und neutrophile Granulozyten, nicht aber mit M2-Makrophagen. Ferner konnte gezeigt werden, dass das „iss mich nicht“ – Signal CD47 auf der Oberfläche der Zielzellen die Aktivierung sowohl von Makrophagen als auch von Granulozyten durch beide Isotypen stark reguliert. In der Zusammenschau konnte zum einen gezeigt werden, dass auch IgG2-Antikörper effektive indirekte Effektormechanismen vermitteln können. Sie sind potente Aktivatoren myeloischer Effektorzellen und im Vergleich zu IgG1-Antikörpern besser in der Aktivierung neutrophiler Granulozyten. Die Aktivitäten der myeloischen Effektorzellen werden zudem stark negativ durch CD47 auf den Tumorzellen reguliert

Saying Hello World with MOLA - A Solution to the TTC 2011 Instructive Case

This paper describes the solution of Hello World transformations in MOLA transformation language. Transformations implementing the task are relatively straightforward and easily inferable from the task specification. The required additional steps related to model import and export are also described.Comment: In Proceedings TTC 2011, arXiv:1111.440

The Inflammatory Response After Ischemic Stroke: Targeting β\u3csub\u3e2\u3c/sub\u3e and β\u3csub\u3e1\u3c/sub\u3e Integrins

Ischemic stroke is a leading cause of death and disability with limited therapeutic options. Resulting inflammatory mechanisms after reperfusion (removal of the thrombus) result in cytokine activation, calcium influx, and leukocytic infiltration to the area of ischemia. In particular, leukocytes migrate toward areas of inflammation by use of integrins, particularly integrins β1 and β2. Integrins have been shown to be necessary for leukocyte adhesion and migration, and thus are of immediate interest in many inflammatory diseases, including ischemic stroke. In this review, we identify the main integrins involved in leukocytic migration following stroke (αLβ2, αDβ2, α4β1, and α5β1) and targeted clinical therapeutic interventions

A General Strategy to Endow Natural Fusion-protein-Derived Peptides with Potent Antiviral Activity

Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy

The EnMAP imaging spectroscopy mission towards operations

EnMAP (Environmental Mapping and Analysis Program) is a high-resolution imaging spectroscopy remote sensing mission that was successfully launched on April 1st, 2022. Equipped with a prism-based dual-spectrometer, EnMAP performs observations in the spectral range between 418.2 nm and 2445.5 nm with 224 bands and a high radiometric and spectral accuracy and stability. EnMAP products, with a ground instantaneous field-of-view of 30 m x 30 m at a swath width of 30 km, allow for the qualitative and quantitative analysis of surface variables from frequently and consistently acquired observations on a global scale. This article presents the EnMAP mission and details the activities and results of the Launch and Early Orbit and Commissioning Phases until November 1st, 2022. The mission capabilities and expected performances for the operational Routine Phase are provided for existing and future EnMAP users

FTIR analysis of hydrogen adsorption on single walled carbon nanotubes

The physisorption of hydrogen on Single Walled Carbon Nanotubes (SWNTs) has been spectroscopically studied by Fourier Transform Infrared Spectroscopy at pressures up to 1000 psi and at ambient temperature. A sample preparation technique has been developed to apply thin films of SWNTs to KBr or Si substrates. The samples showed a broad general absorption which increased with the amount of nanotubes, but it did not show any spectral evidence of the SWNTs or functional groups attached to the nanotubes. It has been shown, that the broad absorption is due to scattering, which can be reduced by up to 50% by applying a refractive index matching liquid. Furthermore baking up to 700° C increases the transmission by up to 90%, which allows the observation of higher sample amounts. Measurements at high pressure showed that the hydrogen dipole moment, induced by a perturbation of the electronic distribution of the H2 molecule due to physisorption on SWNTs, lies below the sensitivity of the system for samples of up to 2.1 mg of nanotubes. At the introduction of hydrogen, water as an impurity of the hydrogen has been observed, which adsorbed on the sample surface. Also an increase in the gaseous CO2 has been detected, which can be caused by adsorped CO2 on the cell wall which is sputtered off by the impact of the hydrogen molecules at high pressure.M.S.Includes bibliographical references (p. 69-71)