@article{WiegeringIsbertDietzetal.2014, author = {Wiegering, Armin and Isbert, Christoph and Dietz, Ulrich A. and Kunzmann, Volker and Ackermann, Sabine and Kerscher, Alexander and Maeder, Uwe and Flentje, Michael and Schlegel, Nicolas and Reibetanz, Joachim and Germer, Christoph-Thomas and Klein, Ingo}, title = {Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence - a retrospective analysis over two decades}, doi = {10.1186/1471-2407-14-816}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110606}, year = {2014}, abstract = {Background The management of rectal cancer (RC) has substantially changed over the last decades with the implementation of neoadjuvant chemoradiotherapy, adjuvant therapy and improved surgery such as total mesorectal excision (TME). It remains unclear in which way these approaches overall influenced the rate of local recurrence and overall survival. Methods Clinical, histological and survival data of 658 out of 662 consecutive patients with RC were analyzed for treatment and prognostic factors from a prospectively expanded single-institutional database. Findings were then stratified according to time of diagnosis in patient groups treated between 1993 and 2001 and 2002 and 2010. Results The study population included 658 consecutive patients with rectal cancer between 1993 and 2010. Follow up data was available for 99.6\% of all 662 treated patients. During the time period between 2002 and 2010 significantly more patients underwent neoadjuvant chemoradiotherapy (17.6\% vs. 60\%) and adjuvant chemotherapy (37.9\% vs. 58.4\%). Also, the rate of reported TME during surgery increased. The rate of local or distant metastasis decreased over time, and tumor related 5-year survival increased significantly with from 60\% to 79\%. Conclusion In our study population, the implementation of treatment changes over the last decade improved the patient's outcome significantly. Improvements were most evident for UICC stage III rectal cancer.}, language = {en} } @article{MetzenmacherVaraljaiHegeduesetal.2020, author = {Metzenmacher, Martin and V{\´a}raljai, Ren{\´a}ta and Heged{\"u}s, Balazs and Cima, Igor and Forster, Jan and Schramm, Alexander and Scheffler, Bj{\"o}rn and Horn, Peter A. and Klein, Christoph A. and Szarvas, Tibor and Reis, Hennig and Bielefeld, Nicola and Roesch, Alexander and Aigner, Clemens and Kunzmann, Volker and Wiesweg, Marcel and Siveke, Jens T. and Schuler, Martin and Lueong, Smiths S.}, title = {Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers12020353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200553}, year = {2020}, abstract = {Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90\% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I-III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers.}, language = {en} } @article{LenzPahlHaucketal.2021, author = {Lenz, Dominic and Pahl, Jens and Hauck, Fabian and Alameer, Seham and Balasubramanian, Meena and Baric, Ivo and Boy, Nikolas and Church, Joseph A. and Crushell, Ellen and Dick, Anke and Distelmaier, Felix and Gujar, Jidnyasa and Indolfi, Giuseppe and Lurz, Eberhard and Peters, Bianca and Schwerd, Tobias and Serranti, Daniele and K{\"o}lker, Stefan and Klein, Christoph and Hoffmann, Georg F. and Prokisch, Holger and Greil, Johann and Cerwenka, Adelheid and Giese, Thomas and Staufner, Christian}, title = {NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency}, series = {Journal of Clinical Immunology}, volume = {41}, journal = {Journal of Clinical Immunology}, number = {8}, issn = {0271-9142}, doi = {10.1007/s10875-021-01110-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308362}, pages = {1781-1793}, year = {2021}, abstract = {Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell-intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of na{\"i}ve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.}, language = {en} }