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https://www.readbyqxmd.com/read/27919179/an-analysis-of-the-role-of-follicular-lymphoma-associated-fibroblasts-to-promote-tumor-cell-viability-following-drug-induced-apoptosis
#1
Annette M Staiger, Jasmin Duppel, Michael A Dengler, Heiko van der Kuip, Matthias C Vöhringer, Walter E Aulitzky, Andreas Rosenwald, German Ott, Heike Horn
Treatment response of follicular lymphomas (FL) is highly variable. We, therefore, investigated the role of FL cancer-associated fibroblasts (CAFs) on tumor cell viability, in particular in response to treatment with cytotoxic drugs. Stromal cells outgrown from FL patients were characterized and pure CAF populations were co-cultivated with FL cells. To analyze fibroblast-mediated effects, cells in co-culture were treated with ABT-737 and Bortezomib. The adherent cell population was positive for all fibroblastic markers tested and showed increased mRNA-expression of the activation marker FAP...
December 6, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27902985/disease-manifestation-and-inflammatory-activity-as-modulators-of-th17-treg-balance-and-rorc-foxp3-methylation-in-systemic-sclerosis
#2
Giovanni Almanzar, Matthias Klein, Marc Schmalzing, Deborah Hilligardt, Nady El Hajj, Hermann Kneitz, Vanessa Wild, Andreas Rosenwald, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Thomas Haaf, Matthias Goebeler, Martina Prelog
BACKGROUND: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. METHODS: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors...
December 1, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27864294/b-cell-receptor-driven-malt1-activity-regulates-myc-signaling-in-mantle-cell-lymphoma
#3
Beiying Dai, Michael Grau, Mélanie Juilland, Pavel Klener, Elisabeth Höring, Jan Molinsky, Gisela Schimmack, Sietse M Aukema, Eva Hoster, Niklas Vogt, Annette M Staiger, Tabea Erdmann, Wendan Xu, Kristian Erdmann, Nicole Dzyuba, Hannelore Madle, Wolfgang E Berdel, Marek Trneny, Martin Dreyling, Korinna Jöhrens, Peter Lenz, Andreas Rosenwald, Reiner Siebert, Alexandar Tzankov, Wolfram Klapper, Ioannis Anagnostopoulos, Daniel Krappmann, German Ott, Margot Thome, Georg Lenz
Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 (CBM) complex that links BCR signaling to the nuclear factor kappa-B (NF-κB) pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo...
November 18, 2016: Blood
https://www.readbyqxmd.com/read/27763811/small-gtpase-proteins-in-macroautophagy
#4
Shu Yang, Anne Rosenwald
Macroautophagy, a highly conserved process in eukaryotic cells, is initiated in response to stress, especially nutrient starvation. Macroautophagy helps cells survive by engulfing proteins and organelles into an unusual double-membraned structure called the autophagosome, which then fuses with the lysosome. Upon degradation of the engulfed contents, the building blocks are recycled for synthesis of new macromolecules. Recent work has demonstrated that construction of the autophagosome requires a variety of small GTPases in variations of their normal roles in membrane traffic...
October 20, 2016: Small GTPases
https://www.readbyqxmd.com/read/27703530/contrary-melanoma-associated-antigen-a-expression-at-the-tumor-front-and-center-a-comparative-analysis-of-stage-i-and-iv-head-and-neck-squamous-cell-carcinoma
#5
Stefan Hartmann, Muna Brisam, Stephan Rauthe, Oliver Driemel, Roman C Brands, Andreas Rosenwald, Alexander C Kübler, Urs D A Müller-Richter
There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27686868/pan-raf-co-operates-with-pi3k-dependent-signalling-and-critically-contributes-to-myeloma-cell-survival-independently-of-mutated-ras
#6
E Müller, S Bauer, T Stühmer, A Mottok, C-J Scholz, T Steinbrunn, D Brünnert, A Brandl, H Schraud, S Kreßmann, A Beilhack, A Rosenwald, R C Bargou, M Chatterjee
Direct therapeutic targeting of oncogenic RAS is currently still impossible due to lack of suitable pharmacological inhibitors. Because specific blockade of druggable RAS effectors might represent an alternative treatment approach, we evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was required to strongly induce apoptosis in MM cell lines, primary MM cells in vitro, and in a syngeneic MM mouse model in vivo...
September 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27670424/frequent-nfkbie-deletions-are-associated-with-poor-outcome-in-primary-mediastinal-b-cell-lymphoma
#7
Larry Mansouri, Daniel Noerenberg, Emma Young, Elena Mylonas, Maysaa Abdulla, Mareike Frick, Fazila Asmar, Viktor Ljungström, Markus Schneider, Kenichi Yoshida, Aron Skaftason, Tatjana Pandzic, Blanca Gonzalez, Anna Tasidou, Nils Waldhueter, Alfredo Rivas-Delgado, Maria Angelopoulou, Marita Ziepert, Christopher Maximilian Arends, Lucile Couronné, Dido Lenze, Claudia D Baldus, Christian Bastard, Jessica Okosun, Jude Fitzgibbon, Bernd Dörken, Hans G Drexler, Damien Roos-Weil, Clemens A Schmitt, Helga D Munch-Petersen, Thorsten Zenz, Martin-Leo Hansmann, Jonathan C Strefford, Gunilla Enblad, Olivier A Bernard, Elisabeth Ralfkiaer, Martin Erlanson, Penelope Korkolopoulou, Magnus Hultdin, Theodora Papadaki, Kirsten Grønbæk, Armando Lopez-Guillermo, Seishi Ogawa, Ralf Küppers, Kostas Stamatopoulos, Niki Stavroyianni, George Kanellis, Andreas Rosenwald, Elias Campo, Rose-Marie Amini, German Ott, Theodoros P Vassilakopoulos, Michael Hummel, Richard Rosenquist, Frederik Damm
We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBε, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%)...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27582569/clinical-impact-of-recurrently-mutated-genes-on-lymphoma-diagnostics-state-of-the-art-and-beyond
#8
REVIEW
Richard Rosenquist, Andreas Rosenwald, Ming-Qing Du, Gianluca Gaidano, Patricia Groenen, Andrew Wotherspoon, Paolo Ghia, Philippe Gaulard, Elias Campo, Kostas Stamatopoulos
Similar to the inherent clinical heterogeneity of most, if not all, lymphoma entities, the genetic landscape of these tumors is markedly complex in the majority of cases, with a rapidly growing list of recurrently mutated genes discovered in recent years by next-generation sequencing technology. Whilst a few genes have been implied to have diagnostic, prognostic and even predictive impact, most gene mutations still require rigorous validation in larger, preferably prospective patient series, to scrutinize their potential role in lymphoma diagnostics and patient management...
September 2016: Haematologica
https://www.readbyqxmd.com/read/27507160/-mediastinal-lymphomas
#9
S Rauthe, A Rosenwald
Lymphomas infiltrating the mediastinum are a challenge for the treating physician as well as for the pathological diagnostics. The clinical scenario is often an emergency situation, while the pathologist is usually confronted only with small biopsy samples. Classical Hodgkin's lymphoma is by far the most frequently occurring lymphoma in the mediastinum and predominantly the nodular sclerosis subtype. In small and very sclerotic specimens it can be difficult to morphologically detect Hodgkin and Reed-Sternberg cells and to identify the characteristic phenotype by immunohistochemistry...
September 2016: Der Pathologe
https://www.readbyqxmd.com/read/27462928/autophagy-in-saccharomyces-cerevisiae-requires-the-monomeric-gtp-binding-proteins-arl1-and-ypt6
#10
Shu Yang, Anne G Rosenwald
Macroautophagy/autophagy is a cellular degradation process that sequesters organelles or proteins into a double-membrane structure called the phagophore; this transient compartment matures into an autophagosome, which then fuses with the lysosome or vacuole to allow hydrolysis of the cargo. Factors that control membrane traffic are also essential for each step of autophagy. Here we demonstrate that 2 monomeric GTP-binding proteins in Saccharomyces cerevisiae, Arl1 and Ypt6, which belong to the Arf/Arl/Sar protein family and the Rab family, respectively, and control endosome-trans-Golgi traffic, are also necessary for starvation-induced autophagy under high temperature stress...
October 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27449515/identification-of-genes-in-candida-glabrata-conferring-altered-responses-to-caspofungin-a-cell-wall-synthesis-inhibitor
#11
Anne G Rosenwald, Gaurav Arora, Rocco Ferrandino, Erica L Gerace, Maedeh Mohammednetej, Waseem Nosair, Shemona Rattila, Amanda Zirzow Subic, Ronda Rolfes
Candida glabrata is an important human fungal pathogen whose incidence continues to rise. Because many clinical isolates are resistant to azole drugs, the drugs of choice to treat such infections are members of the echinocandin family, although there are increasing reports of resistance to these drugs as well. In efforts to better understand the genetic changes that lead to altered responses to echinocandins, we screened a transposon-insertion library of mutants for strains to identify genes that are important for cellular responses to caspofungin, a member of this drug family...
2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27418643/clinicogenetic-risk-models-predict-early-progression-of-follicular-lymphoma-after-first-line-immunochemotherapy
#12
Vindi Jurinovic, Robert Kridel, Annette M Staiger, Monika Szczepanowski, Heike Horn, Martin H Dreyling, Andreas Rosenwald, German Ott, Wolfram Klapper, Andrew D Zelenetz, Paul M Barr, Jonathan W Friedberg, Stephen Ansell, Laurie H Sehn, Joseph M Connors, Randy D Gascoyne, Wolfgang Hiddemann, Michael Unterhalt, David M Weinstock, Oliver Weigert
Follicular lymphoma (FL) is a clinically and molecularly heterogeneous disease. Posttreatment surrogate end points, such as progression of disease within 24 months (POD24) are promising predictors for overall survival (OS) but are of limited clinical value, primarily because they cannot guide up-front treatment decisions. We used the clinical and molecular data from 2 independent cohorts of symptomatic patients in need of first-line immunochemotherapy (151 patients from a German Low-Grade Lymphoma Study Group [GLSG] trial and 107 patients from a population-based registry of the British Columbia Cancer Agency [BCCA]) to validate the predictive utility of POD24, and to evaluate the ability of pretreatment risk models to predict early treatment failure...
August 25, 2016: Blood
https://www.readbyqxmd.com/read/27390358/alterations-of-mirnas-and-mirna-regulated-mrna-expression-in-gc-b-cell-lymphomas-determined-by-integrative-sequencing-analysis
#13
Kebria Hezaveh, Andreas Kloetgen, Stephan H Bernhart, Kunal Das Mahapatra, Dido Lenze, Julia Richter, Andrea Haake, Anke K Bergmann, Benedikt Brors, Birgit Burkhardt, Alexander Claviez, Hans G Drexler, Roland Eils, Siegfried Haas, Steve Hoffmann, Dennis Karsch, Wolfram Klapper, Kortine Kleinheinz, Jan Korbel, Helene Kretzmer, Markus Kreuz, Ralf Küppers, Chris Lawerenz, Ellen Leich, Markus Loeffler, Luisa Mantovani-Loeffler, Cristina López, Alice C McHardy, Peter Möller, Marius Rohde, Philip Rosenstiel, Andreas Rosenwald, Markus Schilhabel, Matthias Schlesner, Ingrid Scholz, Peter F Stadler, Stephan Stilgenbauer, Séphanie Sungalee, Monika Szczepanowski, Lorenz Trümper, Marc A Weniger, Reiner Siebert, Arndt Borkhardt, Michael Hummel, Jessica I Hoell
MicroRNAs are well-established players in posttranscriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNAs/target mRNAs interaction is mostly lacking. Within the International Cancer Genome Consortium Project Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing (ICGC MMML-Seq), we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas...
July 6, 2016: Haematologica
https://www.readbyqxmd.com/read/27389057/combined-copy-number-and-mutation-analysis-identifies-oncogenic-pathways-associated-with-transformation-of-follicular-lymphoma
#14
A Bouska, W Zhang, Q Gong, J Iqbal, A Scuto, J Vose, M Ludvigsen, K Fu, D D Weisenburger, T C Greiner, R D Gascoyne, A Rosenwald, G Ott, E Campo, L M Rimsza, J Delabie, E S Jaffe, R M Braziel, J M Connors, C-I Wu, L M Staudt, F D'Amore, T W McKeithan, W C Chan
Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information...
July 8, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27356265/novel-igh-and-myc-translocation-partners-in-diffuse-large-b-cell-lymphomas
#15
Claudia Otto, René Scholtysik, Roland Schmitz, Markus Kreuz, Claudia Becher, Michael Hummel, Andreas Rosenwald, Lorenz Trümper, Wolfram Klapper, Reiner Siebert, Ralf Küppers
Chromosomal translocations involving an immunoglobulin (IG) locus and a proto-oncogene play a major role in diffuse large B-cell lymphoma (DLBCL) pathogenesis. Recurrent IG translocation partners in DLBCL are the BCL6, BCL2, and MYC genes, but other rare translocation partners are also known. We studied 20 DLBCL with fluorescence in situ hybridization-based evidence for IG heavy chain (IGH) locus-associated translocations not involving BCL6, BCL2, MALT1, or MYC by long distance inverse PCR to identify the translocation partners...
June 29, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27317434/usp9x-stabilizes-xiap-to-regulate-mitotic-cell-death-and-chemoresistance-in-aggressive-b-cell-lymphoma
#16
Katharina Engel, Martina Rudelius, Jolanta Slawska, Laura Jacobs, Behnaz Ahangarian Abhari, Bettina Altmann, Julia Kurutz, Abirami Rathakrishnan, Vanesa Fernández-Sáiz, Andrä Brunner, Bianca-Sabrina Targosz, Felicia Loewecke, Christian Johannes Gloeckner, Marius Ueffing, Simone Fulda, Michael Pfreundschuh, Lorenz Trümper, Wolfram Klapper, Ulrich Keller, Philipp J Jost, Andreas Rosenwald, Christian Peschel, Florian Bassermann
The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression...
2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27270432/vegf-ablation-therapy-reduces-drug-delivery-and-therapeutic-response-in-ecm-dense-tumors
#17
F Röhrig, S Vorlová, H Hoffmann, M Wartenberg, F E Escorcia, S Keller, M Tenspolde, I Weigand, S Gätzner, K Manova, O Penack, D A Scheinberg, A Rosenwald, S Ergün, Z Granot, E Henke
The inadequate transport of drugs into the tumor tissue caused by its abnormal vasculature is a major obstacle to the treatment of cancer. Anti-vascular endothelial growth factor (anti-VEGF) drugs can cause phenotypic alteration and maturation of the tumor's vasculature. However, whether this consistently improves delivery and subsequent response to therapy is still controversial. Clinical results indicate that not all patients benefit from antiangiogenic treatment, necessitating the development of criteria to predict the effect of these agents in individual tumors...
June 6, 2016: Oncogene
https://www.readbyqxmd.com/read/27257180/genome-wide-analysis-of-pediatric-type-follicular-lymphoma-reveals-low-genetic-complexity-and-recurrent-alterations-of-tnfrsf14-gene
#18
Janine Schmidt, Shunyou Gong, Teresa Marafioti, Barbara Mankel, Blanca Gonzalez-Farre, Olga Balagué, Ana Mozos, José Cabeçadas, Jon van der Walt, Daniela Hoehn, Andreas Rosenwald, German Ott, Stefan Dojcinov, Caoimhe Egan, Ferran Nadeu, Joan Enric Ramis-Zaldívar, Guillem Clot, Carmen Bárcena, Vanesa Pérez-Alonso, Volker Endris, Roland Penzel, Carmen Lome-Maldonado, Irina Bonzheim, Falko Fend, Elias Campo, Elaine S Jaffe, Itziar Salaverria, Leticia Quintanilla-Martinez
Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)(-) FL in adults were investigated...
August 25, 2016: Blood
https://www.readbyqxmd.com/read/27246973/rare-snps-in-receptor-tyrosine-kinases-are-negative-outcome-predictors-in-multiple-myeloma
#19
Sarah Keppler, Susann Weiβbach, Christian Langer, Stefan Knop, Jordan Pischimarov, Miriam Kull, Thorsten Stühmer, Torsten Steinbrunn, Ralf Bargou, Hermann Einsele, Andreas Rosenwald, Ellen Leich
Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the "Deutsche Studiengruppe Multiples Myelom"...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27212033/an-important-role-for-myb-muvb-and-its-target-gene-kif23-in-a-mouse-model-of-lung-adenocarcinoma
#20
F Iltzsche, K Simon, S Stopp, G Pattschull, S Francke, P Wolter, S Hauser, D J Murphy, P Garcia, A Rosenwald, S Gaubatz
The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated...
May 23, 2016: Oncogene
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