@article{TonyBurmesterSchulzeKoopsetal.2011, author = {Tony, Hans-Peter and Burmester, Gerd and Schulze-Koops, Hendrik and Grunke, Mathias and Henes, Joerg and K{\"o}tter, Ina and Haas, Judith and Unger, Leonore and Lovric, Svjetlana and Haubitz, Marion and Fischer-Betz, Rebecca and Chehab, Gamal and Rubbert-Roth, Andrea and Specker, Christof and Weinerth, Jutta and Holle, Julia and M{\"u}ller-Ladner, Ulf and K{\"o}nig, Ramona and Fiehn, Christoph and Burgwinkel, Philip and Budde, Klemens and S{\"o}rensen, Helmut and Meurer, Michael and Aringer, Martin and Kieseier, Bernd and Erfurt-Berge, Cornelia and Sticherling, Michael and Veelken, Roland and Ziemann, Ulf and Strutz, Frank and von Wussow, Praxis and Meier, Florian MP and Hunzelmann, Nico and Schmidt, Enno and Bergner, Raoul and Schwarting, Andreas and Eming, R{\"u}diger and Schwarz-Eywill, Michael and Wassenberg, Siegfried and Fleck, Martin and Metzler, Claudia and Zettl, Uwe and Westphal, Jens and Heitmann, Stefan and Herzog, Anna L. and Wiendl, Heinz and Jakob, Waltraud and Schmidt, Elvira and Freivogel, Klaus and D{\"o}rner, Thomas and Hertl, Michael and Stadler, Rudolf}, title = {Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)}, series = {Arthritis Research \& Therapy}, volume = {13}, journal = {Arthritis Research \& Therapy}, number = {R75}, doi = {10.1186/ar3337}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142856}, pages = {1-14}, year = {2011}, abstract = {Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0\% with systemic lupus erythematosus, 15.7\% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1\% multiple sclerosis and 10.0\% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0\% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3\% of patients showed no response, 45.1\% showed a partial response and 41.6\% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm)}, language = {en} } @phdthesis{Fischer2008, author = {Fischer, Julia}, title = {Chromosomale Fluoreszenz-in-situ-Hybridisierung beim Urothelkarzinom; Diagnose, Fr{\"u}herkennung und Verlgeich mit der Urinzytologie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28653}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Das Harnblasenkarzinom ist eines der h{\"a}ufigsten urogenitalen Karzinome. In den letzten Jahren wurden zunehmend neue molekulare Marker entwickelt, um Karzinome nicht-invasiv detektieren zu k{\"o}nnen, darunter die chromosomale Fluoreszenz-in-situ-Hybridisierung. In der vorliegenden Studie sollte die Durchf{\"u}hrbarkeit der Methode an bereits zytologisch aufbereiteten (gef{\"a}rbten) Pr{\"a}paraten untersucht, bereits erhobene zytologische Untersuchungsergebnisse mit den FISH-Resultaten verglichen, zytologisch zweifelhafte Befunde gekl{\"a}rt und retrospektiv festgestellt werden, ob eine im Verlauf beobachtete Karzinomentwicklung (positives follow-up) zu einem fr{\"u}heren Zeitpunkt bei noch negativen zytologischen Resultaten durch die FISH-Methode nachweisbar gewesen w{\"a}re. In die vorliegende Studie gingen 79 zytologische Pr{\"a}parate ein, darunter HE- und Papanicolaou-gef{\"a}rbte Pr{\"a}parate. Alle Pr{\"a}parate wurden nach mehreren Waschschritten in einer Proteasel{\"o}sung inkubiert und danach mit der Sondenmischung des UroVysion™ Bladder Cancer Recurrence Kits inkubiert, die mit zentromerspezifischen Chromosomensonden und einer Lokus-spezifischen Sonde die Chromosomen 3, 7, 17 und den Lokus 9p21 fluoreszenzmarkiert. Anschließend erfolgte die Hybridisierung und das Gegenf{\"a}rben. Bei der Befundung nach Vysis™-Kriterien musste das Pr{\"a}parat f{\"u}r eine positive (maligne) Befundung vier oder mehr der 25 Zellkerne mit einer Zunahme der Signale der Chromosomen 3, 7 oder 17 oder 12 oder mehr Zellkerne mit einem oder keinem Signal f{\"u}r 9p21 aufweisen. Nach den Kriterien der Basler Arbeitsgruppe galt ein Pr{\"a}parat mit 2 oder mehr Zellkernen mit Signalzunahme bei Chromosom 3, 7 und 17 oder bei Verlust eines oder beider 9p2-Signale als maligne. Im Hinblick auf die erbrachten Ergebnisse war FISH nach Vysis-Schema deutlich sensitiver als die Zytologie (79,2 \% vs. 54,2 \%). Die Auswertung nach Basel war gleich sensitiv, jedoch mit 76,4 \% deutlich weniger spezifisch (Vysis-Verfahren 92,7 \%, Zytologie 98,2 \%). Zytologie und FISH waren bei h{\"o}her-gradigen Karzinomen gleich sensitiv (je 100 \%). Die Sensitivit{\"a}t nahm mit dem Grad der Zellaberrationen ab. 91 \% betrug die Sensitivit{\"a}t der FISH bei G2-Karzinomen gegen{\"u}ber 72,7 \% der Zytologie. Daneben kann von einer prognostischen Aussagekraft aktuell falsch-positiver Vysis-Ergebnisse ausgegangen werden. Ungef{\"a}rbte Pr{\"a}parate und HE-gef{\"a}rbte Pr{\"a}parate zeigten sich unabh{\"a}ngig von der Gewinnungsmethode des Zellmaterials als uneingeschr{\"a}nkt zug{\"a}nglich f{\"u}r eine FISH-Auswertung. Papanicolaou-gef{\"a}rbte Routinepr{\"a}parate waren in der Auswertung unbefriedigend mit falsch-negativen Resultaten. Die Kl{\"a}rung zytologisch zweifelhafter Befunde gelang auch mit FISH nur unbefriedigend. Beide Verfahren hatten im schwierig diagnostizierbaren Bereich der niedriggradigen Karzinome Sensitivit{\"a}tseinbußen und kamen bei den G1-Karzinomen auf eine Sensitivit{\"a}t von je 60 \%. H{\"o}hergradige Karzinome (G3) wurden von beiden Verfahren sicher detektiert. Retrospektiv konnte festgestellt werden, dass FISH in vielen F{\"a}llen eine im Verlauf beobachtete Karzinomentwicklung (positives follow-up) zum Zeitpunkt der negativen zytologischen Beurteilung hat nachweisen k{\"o}nnen. Zusammenfassend erwies sich FISH als ein Untersuchungsverfahren mit guter diagnostischer und prognostischer Aussagekraft.}, subject = {FISH}, language = {de} } @article{ČuklinaHahnImakaevetal.2016, author = {Čuklina, Jelena and Hahn, Julia and Imakaev, Maxim and Omasits, Ulrich and F{\"o}rstner, Konrad U. and Ljubimov, Nikolay and Goebel, Melanie and Pessi, Gabriella and Fischer, Hans-Martin and Ahrens, Christian H. and Gelfand, Mikhail S. and Evguenieva-Hackenberg, Elena}, title = {Genome-wide transcription start site mapping of Bradyrhizobium japonicum grown free-living or in symbiosis - a rich resource to identify new transcripts, proteins and to study gene regulation}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, doi = {10.1186/s12864-016-2602-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164565}, pages = {302}, year = {2016}, abstract = {Background Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters. Results A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 \% of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file. Conclusions The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes.}, language = {en} } @article{BallinHotzBourratetal.2019, author = {Ballin, Nadja and Hotz, Alrun and Bourrat, Emmanuelle and K{\"u}sel, Julia and Oji, Vinzenz and Bouadjar, Bakar and Brognoli, Davide and Hickman, Geoffroy and Heinz, Lisa and Vabres, Pierre and Marrakchi, Slaheddine and Leclerc-Mercier, St{\´e}phanie and Irvine, Alan and Tadini, Gianluca and Hamm, Henning and Has, Cristina and Blume-Peytavi, Ulrike and Mitter, Diana and Reitenbach, Marina and Hausser, Ingrid and Zimmer, Andreas D. and Alter, Svenja and Fischer, Judith}, title = {Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4}, series = {Human Mutation}, volume = {40}, journal = {Human Mutation}, number = {12}, doi = {10.1002/humu.23883}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212747}, pages = {2318-2333}, year = {2019}, abstract = {Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa-Like Domain-Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype-phenotype correlations.}, language = {en} } @article{FuxArndtLangenmayeretal.2019, author = {Fux, Robert and Arndt, Daniela and Langenmayer, Martin C. and Schwaiger, Julia and Ferling, Hermann and Fischer, Nicole and Indenbirken, Daniela and Grundhoff, Adam and D{\"o}lken, Lars and Adamek, Mikolaj and Steinhagen, Dieter and Sutter, Gerd}, title = {Piscine orthoreovirus 3 is not the causative pathogen of proliferative darkening syndrome (PDS) of brown trout (Salmo trutta fario)}, series = {Viruses}, volume = {11}, journal = {Viruses}, number = {2}, issn = {1999-4915}, doi = {10.3390/v11020112}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196991}, year = {2019}, abstract = {The proliferative darkening syndrome (PDS) is a lethal disease of brown trout (Salmo trutta fario) which occurs in several alpine Bavarian limestone rivers. Because mortality can reach 100\%, PDS is a serious threat for affected fish populations. Recently, Kuehn and colleagues reported that a high throughput RNA sequencing approach identified a piscine orthoreovirus (PRV) as a causative agent of PDS. We investigated samples from PDS-affected fish obtained from two exposure experiments performed at the river Iller in 2008 and 2009. Using a RT-qPCR and a well-established next-generation RNA sequencing pipeline for pathogen detection, PRV-specific RNA was not detectable in PDS fish from 2009. In contrast, PRV RNA was readily detectable in several organs from diseased fish in 2008. However, similar virus loads were detectable in the control fish which were not exposed to Iller water and did not show any signs of the disease. Therefore, we conclude that PRV is not the causative agent of PDS of brown trout in the rhithral region of alpine Bavarian limestone rivers. The abovementioned study by Kuehn used only samples from the exposure experiment from 2008 and detected a subclinical PRV bystander infection. Work is ongoing to identify the causative agent of PDS.}, language = {en} } @article{FischerDirksKlaussneretal.2022, author = {Fischer, Jonas and Dirks, Johannes and Klaussner, Julia and Haase, Gabriele and Holl-Wieden, Annette and Hofmann, Christine and Hackenberg, Stephan and Girschick, Hermann and Morbach, Henner}, title = {Effect of clonally expanded PD-1\(^h\)\(^i\)\(^g\)\(^h\) CXCR5-CD4+ peripheral T Helper cells on B cell differentiation in the joints of patients with antinuclear antibody-positive juvenile idiopathic arthritis}, series = {Arthritis \& Rheumatology}, volume = {74}, journal = {Arthritis \& Rheumatology}, number = {1}, doi = {10.1002/art.41913}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256607}, pages = {150-162}, year = {2022}, abstract = {Objective Antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the precise role of CD4+ T cells in promoting local B cell activation is unknown. This study was undertaken to determine the phenotype and function of synovial CD4+ T cells that promote aberrant B cell activation in JIA. Methods Flow cytometry was performed to compare the phenotype and cytokine patterns of PD-1\(^h\)\(^i\)\(^g\)\(^h\)CD4+ T cells in the synovial fluid (SF) of patients with JIA and T follicular helper cells in the tonsils of control individuals. TCRVB next-generation sequencing was used to analyze T cell subsets for signs of clonal expansion. The functional impact of these T cell subsets on B cells was examined in cocultures in vitro. Results Multidimensional flow cytometry revealed the expansion of interleukin-21 (IL-21) and interferon-γ (IFNγ)-coexpressing PD-1\(^h\)\(^i\)\(^g\)\(^h\)CXCR5-HLA-DR+CD4+ T cells that accumulate in the joints of ANA-positive JIA patients. These T cells exhibited signs of clonal expansion with restricted T cell receptor clonotypes. The phenotype resembled peripheral T helper (Tph) cells with an extrafollicular chemokine receptor pattern and high T-bet and B lymphocyte-induced maturation protein 1 expression, but low B cell lymphoma 6 expression. SF Tph cells, by provision of IL-21 and IFNy, skewed B cell differentiation toward a CD21\(^l\)\(^o\)\(^w\)\(^/\)\(^-\)CD11c+ phenotype in vitro. Additionally, SF Tph cell frequencies correlated with the appearance of SF CD21\(^l\)\(^o\)\(^w\)\(^/\)\(^-\)CD11c+CD27-IgM- double-negative (DN) B cells in situ.}, language = {en} } @article{AssfalgSeligTolksdorfetal.2020, author = {Assfalg, Volker and Selig, Katharina and Tolksdorf, Johanna and van Meel, Marieke and de Vries, Erwin and Ramsoebhag, Anne-Marie and Rahmel, Axel and Renders, Lutz and Novotny, Alexander and Matevossian, Edouard and Schneeberger, Stefan and Rosenkranz, Alexander R. and Berlakovich, Gabriela and Ysebaert, Dirk and Knops, No{\"e}l and Kuypers, Dirk and Weekers, Laurent and Muehlfeld, Anja and Rump, Lars-Christian and Hauser, Ingeborg and Pisarski, Przemyslaw and Weimer, Rolf and Fornara, Paolo and Fischer, Lutz and Kliem, Volker and Sester, Urban and Stippel, Dirk and Arns, Wolfgang and Hau, Hans-Michael and Nitschke, Martin and Hoyer, Joachim and Thorban, Stefan and Weinmann-Menke, Julia and Heller, Katharina and Banas, Bernhard and Schwenger, Vedat and Nadalin, Silvio and Lopau, Kai and H{\"u}ser, Norbert and Heemann, Uwe}, title = {Repeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis}, series = {Transplant International}, volume = {33}, journal = {Transplant International}, number = {6}, doi = {10.1111/tri.13569}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214161}, pages = {617 -- 631}, year = {2020}, abstract = {In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0\% vs. 84.5\%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7\%) than in 1st DDRT (7.1\%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.}, language = {en} } @article{FischerKnopDanhofetal.2022, author = {Fischer, Julia and Knop, Stefan and Danhof, Sophia and Einsele, Hermann and Keller, Daniela and L{\"o}ffler, Claudia}, title = {The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: a prospective observational study}, series = {BMC Cancer}, volume = {22}, journal = {BMC Cancer}, doi = {10.1186/s12885-022-10101-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300435}, year = {2022}, abstract = {Background Multiple myeloma (MM) is the third most common hematologic malignancy with increasing importance due to improving treatment strategies and long-term outcomes in an aging population. This study aims to analyse influencing factors on health-related quality of life (HRQoL), such as treatment strategies, participation in a clinical trial and patient characteristics like anxiety, depression, gender, and age. A better understanding of the individual factors in context with HRQoL could provide a helpful instrument for clinical decisions. Methods In this prospective observational study, the HRQoL of MM patients with different therapies (first-line and relapse) was quantified by standardized questionnaires (EORTC QLQ-C30 and -MY20) in the context of sociodemographic data, individual anxiety and depressiveness (PHQ-4), and a selected number of clinical parameters and symptoms at defined time-points before, during, and after therapy. Results In total, 70 patients were included in the study. The median age of the study cohort was 62 years. 44\% were female and 56\% were male patients. More than half of the patients were fully active with an ECOG 0. Global health status was significantly higher in patients with first-line treatment and even increased after start of therapy, while the pain level decreased. In contrast, patients with relapsed MM reported a decreasing global health status and increasing pain. Additionally, there was a higher global health status in less anxious/depressive patients. HRQoL decreased significantly after start of chemotherapy in the parameters body image, side effects of treatment, and cognitive functioning. Tandem stem-cell transplantation was not found to be a risk factor for higher impairment of HRQoL. Participation in a clinical study led to an improvement of most aspects of HRQoL. Among others, increased anxiety and depression, female gender, older age, impaired performance status, and recurrent disease can be early indicators for a reduced HRQoL. Conclusion This study showed the importance of regular longitudinal assessments of patient reported outcomes (PROs) in routine clinical care. For the first time, to our knowledge, we were able to demonstrate a potential impact between participation in clinical trials and HRQoL. However, due to frequently restrictive inclusion criteria for clinical trials, these MM patients might not be directly comparable with patients treated within standard therapy concepts. Further studies are needed to clarify the relevance of this preliminary data in order to develop an individualized, patient-centred, therapy concept.}, language = {en} } @phdthesis{Fischer2023, author = {Fischer, Julia Katrin}, title = {Evaluation der Lebensqualit{\"a}t von Patienten mit Multiplem Myelom mittels standardisierter Frageb{\"o}gen der EORTC}, doi = {10.25972/OPUS-31662}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-316628}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Im Rahmen dieser Studie wurde die Lebensqualit{\"a}t (QoL) von Patienten mit Multiplem Myelom zu verschiedenen Therapiezeitpunkten untersucht. Dabei erwies sich die erstmals im Rahmen einer Studie mit Myelompatienten angewandte Kombination aus PHQ-4, EORTC QLQ-C30 und dem spezifischen -MY20 Fragebogen als geeignetes Instrument zur validen Erfassung von {\"A}ngstlichkeit/Depressivit{\"a}t und Lebensqualit{\"a}t. Insgesamt sch{\"a}tzten Erstlinienpatienten, M{\"a}nner und j{\"u}ngere Patienten vor, w{\"a}hrend und nach der Therapie ihre Lebensqualit{\"a}t positiver ein, sodass insbesondere Rezidivpatienten, Frauen und {\"a}ltere Patienten von einer intensivierten therapiebegleitenden supportiven Betreuung profitieren k{\"o}nnten. Es sollte bei der Therapiewahl ber{\"u}cksichtigt werden, dass Erstlinienpatienten zum einen {\"u}ber eine insgesamt bessere allgemeine QoL und geringere Schmerzen als Rezidivpatienten berichteten und zum anderen es durch die systemische Therapie bei diesen zu einer weiteren Verbesserung kommen kann. Unabh{\"a}ngig hiervon korrelierte der ECOG-Status signifikant mit der QoL und sollte daher regelm{\"a}ßig erhoben werden. W{\"a}hrend der Therapie kam es bei Myelompatienten v.a. zu einer negativeren Wahrnehmung des eigenen K{\"o}rperbilds, einer Abnahme der kognitiven Funktion und einer Zunahme der Therapienebenwirkungen, sodass interdisziplin{\"a}re Behandlerteams neben einem optimalen Nebenwirkungsmanagement auch in der klinischen Routine noch nicht so fest etablierte Ressourcen ber{\"u}cksichtigen sollten, wie z.B. psychoedukative Interventionen, Entspannungsverfahren oder auch kognitives Training. Eine der wichtigsten Erkenntnisse der Studie war die signifikant reduzierte Lebensqualit{\"a}t bei Patienten mit vermehrter {\"A}ngstlichkeit/Depressivit{\"a}t, die die Notwendigkeit eines regelm{\"a}ßigen Screenings in der klinischen Routine aufzeigt, um Risikopatienten entsprechend zu identifizieren. Trotz der vermuteten Lebensqualit{\"a}tsbeeinflussung durch die intensivere, l{\"a}ngere Therapie, zeigten sich bei Tandemtransplantierten nicht mehr Lebensqualit{\"a}tsvariablen signifikant negativ beeinflusst als beim Gesamtkollektiv, sodass diese Beobachtung eine wertvolle Entscheidungshilfe f{\"u}r Patienten sein k{\"o}nnte, die aus Sorge vor einer reduzierten Lebensqualit{\"a}t transplantationsbasierten Konzepten zur{\"u}ckhaltend gegen{\"u}berstehen. Unter Ber{\"u}cksichtigung der o.g. Limitationen, konnte zus{\"a}tzlich eine deutliche positive Beeinflussung der Lebensqualit{\"a}t durch Teilnahme an klinischen Therapiestudien aufgezeigt werden, sodass Patienten evtl. von einer noch intensiveren multiprofessionellen Begleitung wie sie in Studiensettings gegeben ist profitieren k{\"o}nnten.}, subject = {Lebensqualit{\"a}t}, language = {de} } @article{HaakeHaackSchaeferetal.2023, author = {Haake, Markus and Haack, Beatrice and Sch{\"a}fer, Tina and Harter, Patrick N. and Mattavelli, Greta and Eiring, Patrick and Vashist, Neha and Wedekink, Florian and Genssler, Sabrina and Fischer, Birgitt and Dahlhoff, Julia and Mokhtari, Fatemeh and Kuzkina, Anastasia and Welters, Marij J. P. and Benz, Tamara M. and Sorger, Lena and Thiemann, Vincent and Almanzar, Giovanni and Selle, Martina and Thein, Klara and Sp{\"a}th, Jacob and Gonzalez, Maria Cecilia and Reitinger, Carmen and Ipsen-Escobedo, Andrea and Wistuba-Hamprecht, Kilian and Eichler, Kristin and Filipski, Katharina and Zeiner, Pia S. and Beschorner, Rudi and Goedemans, Renske and Gogolla, Falk Hagen and Hackl, Hubert and Rooswinkel, Rogier W. and Thiem, Alexander and Romer Roche, Paula and Joshi, Hemant and P{\"u}hringer, Dirk and W{\"o}ckel, Achim and Diessner, Joachim E. and R{\"u}diger, Manfred and Leo, Eugen and Cheng, Phil F. and Levesque, Mitchell P. and Goebeler, Matthias and Sauer, Markus and Nimmerjahn, Falk and Schuberth-Wagner, Christine and Felten, Stefanie von and Mittelbronn, Michel and Mehling, Matthias and Beilhack, Andreas and van der Burg, Sjoerd H. and Riedel, Angela and Weide, Benjamin and Dummer, Reinhard and Wischhusen, J{\"o}rg}, title = {Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-39817-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357333}, year = {2023}, abstract = {Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.}, language = {en} }