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https://www.readbyqxmd.com/read/29122756/foxp1-expression-is-a-prognostic-biomarker-in-follicular-lymphoma-treated-with-rituximab-containing-regimens
#1
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of seven genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2- and MEF2B-mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in a total of 763 tissue biopsies...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29092062/gemcitabine-based-chemotherapy-in-adrenocortical-carcinoma-a-multicenter-study-of-efficacy-and-predictive-factors
#2
Judith E K Henning, Timo Deutschbein, Barbara Altieri, Sonja Steinhauer, Stefan Kircher, Silviu Sbiera, Vanessa Wild, Wiebke Schlötelburg, Matthias Kroiss, Paola Perotti, Andreas Rosenwald, Alfredo Berruti, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29079592/inhibition-of-focal-adhesion-kinase-overcomes-resistance-of-mantle-cell-lymphoma-to-ibrutinib-in-the-bone-marrow-microenvironment
#3
Martina Rudelius, Mathias Tillmann Rosenfeldt, Ellen Leich, Hilka Rauert-Wunderlich, Antonio Giovanni Solimando, Andreas Beilhack, German Ott, Andreas Rosenwald
Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells cocultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi based focal adhesion kinase silencing was performed...
October 27, 2017: Haematologica
https://www.readbyqxmd.com/read/29064484/jam-a-as-a-prognostic-factor-and-new-therapeutic-target-in-multiple-myeloma
#4
A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis...
September 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29052597/syk-expression-in-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma
#5
Grit Mutzbauer, Katja Maurus, Clara Buszello, Jordan Pischimarov, Sabine Roth, Andreas Rosenwald, Andreas Chott, Eva Geissinger
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathy associated T-cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T-cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T-cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29026624/first-case-of-human-peritoneal-cysticercosis-mimicking-peritoneal-carcinosis-necessity-of-laparoscopy-and-histologic-assessment-for-the-correct-diagnosis
#6
Martina Rudelius, Klaus Brehm, Martin Poelcher, Christoph Spinner, Andreas Rosenwald, Clarissa Prazeres da Costa
Introduction. Correct diagnosis of peritoneal infectious disease can be extremely difficult due to non-specific clinical features. Thus, careful assessment with thorough histopathological work-up is essential. Here, we report the first case of human peritoneal cysticercosis mimicking peritoneal carcinosis. Case presentation. The patient presented with recurring ascites and a tumour in the Douglas cavity accompanied by elevated tumour markers. There were no signs of systemic infection. On laparoscopy, the tumour was resected completely...
June 2017: JMM Case Reports
https://www.readbyqxmd.com/read/28844114/the-clinicopathologic-spectrum-of-mature-aggressive-b-cell-lymphomas
#7
REVIEW
Lisa Rimsza, Stefania Pittaluga, Stephan Dirnhofer, Christiane Copie-Bergman, Laurence de Leval, Fabio Facchetti, Stefano Pileri, Andreas Rosenwald, Andrew Wotherspoon, Falko Fend
Our understanding of mature aggressive B cell lymphomas has evolved significantly in the last years as reflected in the 2016 update of the WHO lymphoma classification. A main topic of the 2016 European Association for Haematopathology/Society of Hematopathology lymphoma workshop in Basel therefore was the clinicopathological spectrum of mature aggressive B cell lymphomas with the exception of conventional diffuse large B cell lymphoma. In this review, we summarize two sessions dedicated to "high-grade B cell lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (so-called double/triple-hit lymphomas)" and "high-grade B cell lymphomas, NOS" as defined in the 2016 update of the WHO lymphoma classification, Burkitt lymphoma and related neoplasms, and terminally differentiated aggressive B cell lymphomas...
October 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28838257/advanced-patient-age-at-diagnosis-of-diffuse-large-b-cell-lymphoma-is-associated-with-molecular-characteristics-including-abc-subtype-and-high-expression-of-myc
#8
Ulrike Paul, Julia Richter, Christiane Stuhlmann-Laiesz, Markus Kreuz, Inga Nagel, Heike Horn, Annette M Staiger, Sietse M Aukema, Michael Hummel, German Ott, Rainer Spang, Andreas Rosenwald, Alfred C Feller, Sergio Cogliatti, Harald Stein, Martin-Leo Hansmann, Peter Moller, Monika Szczepanowski, Birgit Burkhardt, Michael Pfreundschuh, Norbert Schmitz, Markus Loeffler, Lorenz Trümper, Reiner Siebert, Wolfram Klapper
The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age being patient age at diagnosis an adverse prognostic factor. However, elderly patients are often underrepresented in common studies. To investigate the effect between age and biological characteristics in DLBCL, we analyzed data of 1534 patients encompassing all adult age groups, enriched for the age ≥75 years. Follicular lymphoma (FL) grade 3B with histopathological characteristics of DLBCLs were included. Gender, centroblastic cytology, FL grade 3B morphology, CD10 expression, and ABC/non-GCB-subtype were significantly associated with age after correction for multiple testing and after adjusting for cohorts...
August 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28801451/adult-high-grade-b-cell-lymphoma-with-burkitt-lymphoma-signature-genomic-features-and-potential-therapeutic-targets
#9
Alyssa Bouska, Chengfeng Bi, Waseem Lone, Weiwei Zhang, Ambreen Kedwaii, Tayla Heavican, Cynthia M Lachel, Jiayu Yu, Roberto Ferro, Nanees Eldorghamy, Timothy C Greiner, Julie Vose, Dennis D Weisenburger, Randy D Gascoyne, Andreas Rosenwald, German Ott, Elias Campo, Lisa M Rimsza, Elaine S Jaffe, Rita M Braziel, Reiner Siebert, Rodney R Miles, Sandeep Dave, Anupama Reddy, Jan Delabie, Louis M Staudt, Joo Y Song, Timothy W McKeithan, Kai Fu, Michael Green, Wing C Chan, Javeed Iqbal
The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/28695297/histiocytic-and-dendritic-cell-neoplasms-what-have-we-learnt-by-studying-67-cases
#10
Fabio Facchetti, Stefano Aldo Pileri, Luisa Lorenzi, Valentina Tabanelli, Lisa Rimsza, Stefania Pittaluga, Stephan Dirnhofer, Christiane Copie-Bergman, Laurence de Leval, Andreas Rosenwald, Andrew Wotherspoon, Falko Fend
Tumors derived from histiocytic and dendritic cells encompass a large and heterogeneous group of neoplastic and reactive conditions, and their diagnosis is challenging both for pathologists and clinicians. Diagnosis is based on morphological and phenotypical findings, but hybrid features are not uncommon. Furthermore, recent studies uncovered the molecular mechanisms driving some of these tumors, improving diagnostic adequacy, and providing the basis for effective therapeutic breakthroughs.Sixty-seven cases were submitted to the accessory cell and histiocytic neoplasms session at the European Association of Haematopathology/Society for Hematopathology workshop 2016 held in Basel, Switzerland...
October 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28614910/tp53-mutation-and-survival-in-aggressive-b-cell-lymphoma
#11
RANDOMIZED CONTROLLED TRIAL
Thorsten Zenz, Markus Kreuz, Maxi Fuge, Wolfram Klapper, Heike Horn, Annette M Staiger, Doris Winter, Hanne Helfrich, Jennifer Huellein, Martin-Leo Hansmann, Harald Stein, Alfred Feller, Peter Möller, Norbert Schmitz, Lorenz Trümper, Markus Loeffler, Reiner Siebert, Andreas Rosenwald, German Ott, Michael Pfreundschuh, Stephan Stilgenbauer
TP53 is mutated in 20-25% of aggressive B-cell lymphoma (B-NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B-NHL, we investigated TP53 gene mutations within the RICOVER-60 trial. Of 1,222 elderly patients (aged 61-80 years) enrolled in the study and randomized to six or eight cycles of CHOP-14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations...
October 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28599276/targeting-cxcr4-with-68-ga-pentixafor-a%C3%A2-suitable-theranostic-approach-in-pleural-mesothelioma
#12
Constantin Lapa, Stefan Kircher, Andreas Schirbel, Andreas Rosenwald, Saskia Kropf, Theo Pelzer, Thorsten Walles, Andreas K Buck, Wolfgang A Weber, Hans-Juergen Wester, Ken Herrmann, Katharina Lückerath
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [(68)Ga]Pentixafor in malignant pleural mesothelioma.Six patients with pleural mesothelioma underwent [(68)Ga]Pentixafor-PET/CT. 2'-[18F]fluoro-2'-deoxy-D-glucose ([18F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference...
May 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573510/b-cell-lymphomas-with-discordance-between-pathological-features-and-clinical-behavior
#13
Laurence de Leval, Christiane Copie-Bergman, Andreas Rosenwald, Lisa Rimsza, Stefania Pittaluga, Bettina Bisig, Stefan Dirnhofer, Fabio Facchetti, Stefano Pileri, Falko Fend, Andrew Wotherspoon
B-cell lymphomas encompass a large number of disease entities clinically ranging from indolent to aggressive. The defining pathological features usually predict clinical course, with small and large B-cell lymphomas correlating to low-grade vs high-grade features, but discordant situations may be encountered. Two sessions of the workshop of the XVIII meeting of the European Association for Haematopathology (EAHP) held in Basel in 2016 addressed this topic. One session illustrated various facets of "aggressiveness" in indolent lymphomas, either peculiar clinical manifestations, cytological variants, or unusual genetic features, as well as several examples of progression or transformation to a more aggressive disease...
October 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28533310/mutations-of-map2k1-are-frequent-in-pediatric-type-follicular-lymphoma-and-result-in-erk-pathway-activation
#14
Janine Schmidt, Joan Enric Ramis-Zaldivar, Ferran Nadeu, Blanca Gonzalez-Farre, Alba Navarro, Caoimhe Egan, Ivonne Aidee Montes-Mojarro, Teresa Marafioti, Jose Cabeçadas, Jon van der Walt, Stefan Dojcinov, Andreas Rosenwald, German Ott, Irina Bonzheim, Falko Fend, Elias Campo, Elaine S Jaffe, Itziar Salaverria, Leticia Quintanilla-Martinez
Pediatric-type follicular lymphoma (PTFL) is a B-cell lymphoma with distinctive clinicopathological features. Recently, recurrent genetic alterations of potential importance for its pathogenesis that disrupt pathways associated with the germinal center reaction (TNFRSF14, IRF8), immune escape (TNFRSF14), and anti-apoptosis (MAP2K1) have been described. In an attempt to shed more light onto the pathogenesis of PTFL, an integrative analysis of these mutations was undertaken in a large cohort of 43 cases previously characterized by targeted next-generation sequencing and copy number array...
July 20, 2017: Blood
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
#15
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
#16
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 W 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...
July 1, 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
#17
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...
May 20, 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
#18
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
#19
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
#20
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...
March 2017: Der Pathologe
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