TY  - JOUR
A1  - Stephan, Marlene
A1  - Tascilar, Koray
A1  - Yalcin-Mutlu, Melek
A1  - Hagen, Melanie
A1  - Haschka, Judith
A1  - Reiser, Michaela
A1  - Hartmann, Fabian
A1  - Kleyer, Arnd
A1  - Hueber, Axel J.
A1  - Manger, Bernhard
A1  - Figueiredo, Camille
A1  - Cobra, Jayme Fogagnolo
A1  - Tony, Hans-Peter
A1  - Finzel, Stephanie
A1  - Kleinert, Stefan
A1  - Wendler, Jörg
A1  - Schuch, Florian
A1  - Ronneberger, Monika
A1  - Feuchtenberger, Martin
A1  - Fleck, Martin
A1  - Manger, Karin
A1  - Ochs, Wolfgang
A1  - Schmitt-Haendle, Matthias
A1  - Lorenz, Hannes Martin
A1  - Nüsslein, Hubert
A1  - Alten, Rieke
A1  - Henes, Joerg
A1  - Krüger, Klaus
A1  - Schett, Georg
A1  - Rech, Jürgen
T1  - Physical function of RA patients tapering treatment — a post hoc analysis of the randomized controlled RETRO trial
JF  - Journal of Clinical Medicine
N2  - Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.
KW  - HAQ
KW  - Rheumatoid Arthritis
KW  - PROM’s
KW  - DMARD
KW  - DAS28
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319349
SN  - 2077-0383
VL  - 12
IS  - 11
ER  - 
TY  - JOUR
A1  - Watzling, Martin
A1  - Klaus, Lorenz
A1  - Weidemeier, Tamara
A1  - Horder, Hannes
A1  - Ebert, Regina
A1  - Blunk, Torsten
A1  - Bauer-Kreisel, Petra
T1  - Three-dimensional breast cancer model to investigate CCL5/CCR1 expression mediated by direct contact between breast cancer cells and adipose-derived stromal cells or adipocytes
JF  - Cancers
N2  - The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell–cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor–stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell–cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer.
KW  - 3D breast cancer model
KW  - adipose-derived stromal cells
KW  - adipocytes
KW  - adipose tissue
KW  - spheroids
KW  - co-culture
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-362502
SN  - 2072-6694
VL  - 15
IS  - 13
ER  -