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https://www.readbyqxmd.com/read/28411252/prognostic-relevance-of-cd163-and-cd8-combined-with-ezh2-and-gain-of-chromosome-18-in-follicular-lymphoma-a-study-by-the-lunenburg-lymphoma-biomarker-consortium
#1
Wendy B C Stevens, Matias Mendeville, Robert Redd, Andrew J Clear, Reno Bladergroen, Maria Calaminici, Andreas Rosenwald, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Luc Xerri, Gilles Salles, Wolfram Klapper, Michael Phreundschuh, Andrew Jack, Randy D Gascoyne, Yasodha Natkunam, Ranjana Advani, Eva Kimby, Birgitta Sander, Laurie Sehn, Anton Hagenbeek, John Raemaekers, John Gribben, Marie Jose' Kersten, Bauke Ylstra, Edie Weller, Daphne de Jong
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries; early failure: progression or lymphoma-related death <2 years versus long remission: response duration of >5 years...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28398499/outcome-of-elderly-patients-with-diffuse-large-b-cell-lymphoma-treated-with-r-chop-results-from-the-uk-ncri-r-chop14v21-trial-with-combined-analysis-of-molecular-characteristics-with-the-dshnhl-ricover-60-trial
#2
A Kühnl, D Cunningham, N Counsell, E A Hawkes, W Qian, P Smith, N Chadwick, A Lawrie, P Mouncey, A Jack, C Pocock, K M Ardeshna, J Radford, A McMillan, J Davies, D Turner, A Kruger, P Johnson, J Gambell, A Rosenwald, G Ott, H Horn, M Ziepert, M Pfreundschuh, D Linch
BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up...
April 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28291392/new-molecular-assay-for-the-proliferation-signature-in-mantle-cell-lymphoma-applicable-to-formalin-fixed-paraffin-embedded-biopsies
#3
David W Scott, Pau Abrisqueta, George W Wright, Graham W Slack, Anja Mottok, Diego Villa, Pedro Jares, Hilka Rauert-Wunderlich, Cristina Royo, Guillem Clot, Magda Pinyol, Merrill Boyle, Fong Chun Chan, Rita M Braziel, Wing C Chan, Dennis D Weisenburger, James R Cook, Timothy C Greiner, Kai Fu, German Ott, Jan Delabie, Erlend B Smeland, Harald Holte, Elaine S Jaffe, Christian Steidl, Joseph M Connors, Randy D Gascoyne, Andreas Rosenwald, Louis M Staudt, Elias Campo, Lisa M Rimsza
Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker-the proliferation signature-using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies. Methods Forty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard...
March 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28188172/t-cell-repertoires-in-refractory-coeliac-disease
#4
Julia Ritter, Karin Zimmermann, Korinna Jöhrens, Stefanie Mende, Anke Seegebarth, Britta Siegmund, Steffen Hennig, Kremena Todorova, Andreas Rosenwald, Severin Daum, Michael Hummel, Michael Schumann
OBJECTIVE: Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis...
February 10, 2017: Gut
https://www.readbyqxmd.com/read/28125644/srf-and-mkl1-independently-inhibit-brown-adipogenesis
#5
Matthias Rosenwald, Vissarion Efthymiou, Lennart Opitz, Christian Wolfrum
Active brown adipose tissue is responsible for non-shivering thermogenesis in mammals which affects energy homeostasis. The molecular mechanisms underlying this activation as well as the formation and activation of brite adipocytes have gained increasing interest in recent years as they might be utilized to regulate systemic metabolism. We show here that the transcriptional regulators SRF and MKL1 both act as repressors of brown adipogenesis. Loss-of-function of these transcription factors leads to a significant induction of brown adipocyte differentiation, increased levels of UCP1 and other thermogenic genes as well as increased respiratory function, while SRF induction exerts the opposite effects...
2017: PloS One
https://www.readbyqxmd.com/read/28120026/-blast-like-tumor-tissue-in-cervical-lymph-node-with-expression-of-placental-alkaline-phosphatase
#6
C Fellbaum, S Kircher, U Oehler, R Blessing, A Rosenwald
We report a case of ALK1-positive anaplastic large cell lymphoma with expression of placental alkaline phosphatase (PLAP) in many tumor cells. Initially, due to the positivity of tumor cells for CD30 and PLAP, lymph node metastasis of a germ cell neoplasm was discussed. Anaplastic large cell lymphomas of T‑cell lineage form a group of rare non-Hodgkin lymphomas with heterogeneous morphological and immunohistochemical appearance. They may imitate other neoplasms, such as large cell B‑cell lymphomas, metastasis of a carcinoma, melanoma, embryonal carcinoma or seminoma, rhabdomyosarcoma and inflammatory myofibroblastic tumor...
January 24, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28119525/frequency-of-regulatory-t-cells-determines-the-outcome-of-the-t-cell-engaging-antibody-blinatumomab-in-patients-with-b-precursor-all
#7
J Duell, M Dittrich, T Bedke, T Mueller, F Eisele, A Rosenwald, L Rasche, E Hartmann, T Dandekar, H Einsele, M S Topp
Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab...
February 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28077739/the-emergence-of-undergraduate-majors-in-global-health-systematic-review-of-programs-and-recommendations-for-future-directions
#8
Paul K Drain, Charles Mock, David Toole, Anne Rosenwald, Megan Jehn, Thomas Csordas, Laura Ferguson, Caryl Waggett, Chinekwu Obidoa, Judith N Wasserheit
Global health education has been expanding rapidly and several universities have created an undergraduate major degree (bachelor's degree) in global heath or global health studies. Because there are currently no national guidelines for undergraduate degrees in global health, each of these programs was developed along individual lines. To guide the development of future global health majors, we conducted a systematic review of undergraduate majors in global health. We identified eight programs and invited program directors or representatives to a symposium at the Consortium of Universities for Global Health 2016 conference to review their existing undergraduate major in global health and to discuss lessons learned and recommendations for other colleges and universities seeking to develop undergraduate degrees in global health...
January 11, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28064214/hsp90-promotes-burkitt-lymphoma-cell-survival-by-maintaining-tonic-b-cell-receptor-signaling
#9
Roland Walter, Kuan-Ting Pan, Carmen Doebele, Federico Comoglio, Katarzyna Tomska, Hanibal Bohnenberger, Ryan M Young, Laura Jacobs, Ulrich Keller, Halvard Bönig, Michael Engelke, Andreas Rosenwald, Henning Urlaub, Louis M Staudt, Hubert Serve, Thorsten Zenz, Thomas Oellerich
Burkitt lymphoma (BL) is an aggressive B-cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Because of their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/28030838/livin-birc7-expression-as-malignancy-marker-in-adrenocortical-tumors
#10
Barbara Altieri, Silviu Sbiera, Silvia Della Casa, Isabel Weigand, Vanessa Wild, Sonja Steinhauer, Guido Fadda, Arkadius Kocot, Michaela Bekteshi, Egle M Mambretti, Andreas Rosenwald, Alfredo Pontecorvi, Martin Fassnacht, Cristina L Ronchi
Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG)...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27974437/a-high-copy-suppressor-screen-for-autophagy-defects-in-saccharomyces-arl1%C3%AE-and-ypt6%C3%AE-strains
#11
Shu Yang, Anne Rosenwald
In Saccharomyces cerevisiae, Arl1 and Ypt6, two small GTP-binding proteins that regulate membrane traffic in the secretory and endocytic pathways, are also necessary for autophagy. To gain information about potential partners of Arl1 and Ypt6 specifically in autophagy, we carried out a high copy number suppressor screen to identify genes that when overexpressed suppress the rapamycin sensitivity phenotype of arl1Δ and ypt6Δ strains at 37°C. From the screen results, we selected COG4, SNX4, TAX4, IVY1, PEP3, SLT2 and ATG5, either membrane traffic or autophagy regulators, to further test whether they can suppress the specific autophagy defects of arl1Δ and ypt6Δ strains...
December 14, 2016: G3: Genes—Genomes—Genetics
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
#12
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...
August 2017: 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
#13
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...
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
#14
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 complex that links BCR signaling to the 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...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/27763811/small-gtpase-proteins-in-macroautophagy
#15
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
#16
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
#17
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 human MM cell lines (HMCLs), in primary MM cells in vitro, and in a syngeneic MM mouse model in vivo...
April 2017: 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
#18
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
#19
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
#20
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
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