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Richters transformation

Elisabeth Richter, Silvia Berkner, Ina Ebert, Bernhard Förster, Nadin Graf, Monika Herrchen, Ute Kühnen, Jörg Römbke, Markus Simon
BACKGROUND: Residues of veterinary medicinal products (VMPs) enter the environment via application of manure onto agricultural areas where in particular antibiotics can cause phytotoxicity. Terrestrial plant tests according to OECD guideline 208 are part of the environmental risk assessment of VMPs. However, this standard approach might not be appropriate for VMPs which form non-extractable residues or transformation products in manure and manure-amended soil. Therefore, a new test design with a more realistic exposure scenario via manure application is needed...
2016: Environmental Sciences Europe
Davide Rossi
Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate for RS is ∼0.5% per year of observation. In the presence of clinical suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. Molecular lesions of tumor suppression regulators (TP53), cell cycle (CDKN2A) and cell proliferation (NOTCH1, MYC) overall account for ∼90% of RS and may be responsible for its aggressive clinical phenotype...
March 2016: Best Practice & Research. Clinical Haematology
Tahereh Javaheri, Zahra Kazemi, Jan Pencik, Ha Tt Pham, Maximilian Kauer, Rahil Noorizadeh, Barbara Sax, Harini Nivarthi, Michaela Schlederer, Barbara Maurer, Maximillian Hofbauer, Dave Nt Aryee, Marc Wiedner, Eleni M Tomazou, Malcolm Logan, Christine Hartmann, Jan P Tuckermann, Lukas Kenner, Mario Mikula, Helmut Dolznig, Aykut Üren, Günther H Richter, Florian Grebien, Heinrich Kovar, Richard Moriggl
Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling...
October 13, 2016: Cell Death & Disease
Emily C Ayers, Anthony R Mato
Richter's transformation (RT) is the transformation of chronic lymphocytic leukemia (CLL) into rapidly progressive B-cell lymphoma. This disease has long been recognized as a difficult-to-treat illness with poor survival outcomes. Although the incidence of RT has been well documented in previous studies, less is understood in the era of novel therapeutics, such as kinase inhibitors (KIs). The present review discusses the current risk factors, incidence, and outcomes of patients with RT in the modern era of KI therapy...
September 8, 2016: Clinical Lymphoma, Myeloma & Leukemia
Bin Wu, Kimberly Ingersoll, Catherine Rehder, Endi Wang
Chronic lymphocytic leukemia (CLL) is an indolent mature B-cell neoplasm. During a prolonged disease course, a secondary B-cell neoplasm may arise in some patients, the most common example being the clonal evolution of CLL to diffuse large B-cell lymphoma, which is referred to as Richter transformation. Secondary de novo mature B-cell neoplasms arising in a patient with pre-existing CLL have been described; however, B-lymphoblastic leukemia (B-ALL) developing in untreated CLL is rare, and its clonal relationship to the primary neoplasm has been an interesting issue...
September 22, 2016: Pathology, Research and Practice
Naveen Pemmaraju, Preetesh Jain, L Jeffrey Medeiros, Jeffrey L Jorgenson, Nitin Jain, Jason Willis, Dimitrios P Kontoyiannis, Zeev Estrov, William Wierda
No abstract text is available yet for this article.
September 27, 2016: American Journal of Hematology
Mohamed A Kharfan-Dabaja, Ambuj Kumar, Mehdi Hamadani, Stephan Stilgenbauer, Paolo Ghia, Claudio Anasetti, Peter Dreger, Emili Montserrat, Miguel-Angel Perales, Edwin P Alyea, Farrukh T Awan, Ernesto Ayala, Jacqueline C Barrientos, Jennifer R Brown, Januario Castro, Richard R Furman, John Gribben, Brian T Hill, Mohamad Mohty, Carol Moreno, Susan O'Brien, Steven Z Pavletic, Javier Pinilla-Ibarz, Nishitha M Reddy, Mohamed Sorror, Christopher Bredeson, Paul Carpenter, Bipin N Savani
We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations...
September 19, 2016: Biology of Blood and Marrow Transplantation
Jun Yi, Adam L O Campbell, George B Richter-Addo
Bacteria utilize a heme/non-heme enzyme system to detoxify nitric oxide (NO) to N2O. In order to probe the capacity of a single-heme system to mediate this NO-to-N2O transformation, various scenarios for addition of electrons, protons, and a second NO molecule to a heme nitrosyl to generate N2O were explored by density functional theory calculations. We describe, utilizing this single-heme system, several stepwise intermediates along pathways that enable the critical N-N bond formation step yielding the desired Fe-N2O product...
September 16, 2016: Nitric Oxide: Biology and Chemistry
Roman C Brands, Olga Köhler, Stephan Rauthe, Stefan Hartmann, Harald Ebhardt, Axel Seher, Christian Linz, Alexander C Kübler, Urs D A Müller-Richter
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common tumor entity worldwide. Unfortunately, the multimodal treatment consisting of surgery, radiation, and chemotherapy does not show the desired efficacy. The intent of this study was to evaluate the sensitivity and specificity of an oral brush biopsy in combination with glucose transporter (GLUT)-1 staining in identifying premalignant and malignant lesions. METHODS: A total of 72 patients were included in the study, divided into four diagnostic subgroups (24 healthy, 15 carcinoma, 18 leukoplakia, 15 oral lichen planus)...
September 8, 2016: Clinical Oral Investigations
Shruti Sharma, Natalie Galanina, Ailin Guo, Jimmy Lee, Sabah Kadri, Charles Van Slambrouck, Bradley Long, Weige Wang, Mei Ming, Larissa V Furtado, Jeremy P Segal, Wendy Stock, Girish Venkataraman, Wei-Jen Tang, Pin Lu, Y Lynn Wang
Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naïve chronic lymphocytic leukemia (CLL). However, about 25% of patients discontinue ibrutinib therapy at a median follow-up of 20 months and many patients discontinue the treatment due to leukemia progression or Richter transformation. Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance...
September 10, 2016: Oncotarget
Anthony R Mato, Chadi Nabhan, Paul M Barr, Chaitra S Ujjani, Brian T Hill, Nicole Lamanna, Alan P Skarbnik, Christina Howlett, Jeffrey J Pu, Alison R Sehgal, Lauren E Strelec, Alexandra Vandegrift, Danielle M Fitzpatrick, Clive S Zent, Tatyana Feldman, Andre Goy, David F Claxton, Spencer Henick Bachow, Gurbakhash Kaur, Jakub Svoboda, Sunita Dwivedy Nasta, David Porter, Daniel J Landsburg, Stephen J Schuster, Bruce D Cheson, Pavel Kiselev, Andrew M Evens
B Cell receptor (BCR) kinase inhibitor (KI) therapy represents a paradigm shift in Chronic Lymphocytic Leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 CLL patients (ibrutinib=143; idelalisib=35) who discontinued KI therapy. We examined responses, toxicity, post-KI therapies, and overall survival (OS). Patients had a median of 3 prior therapies (range 0-11); del17p (34%), p53 mutation (27%), del11q (33%), and complex karyotype (29%)...
September 6, 2016: Blood
Yvette Meissner, Angela Zink, Jörn Kekow, Karin Rockwitz, Anke Liebhaber, Silke Zinke, Kerstin Gerhold, Adrian Richter, Joachim Listing, Anja Strangfeld
BACKGROUND: The aim was to estimate the impact of individual risk factors and treatment with various disease-modifying antirheumatic drugs (DMARDs) on the incidence of myocardial infarction (MI) in patients with rheumatoid arthritis (RA). METHODS: We analysed data from 11,285 patients with RA, enrolled in the prospective cohort study RABBIT, at the start of biologic (b) or conventional synthetic (cs) DMARDs. A nested case-control study was conducted, defining patients with MI during follow-up as cases...
2016: Arthritis Research & Therapy
Anne Richter, Ulrica von Thiele Schwarz, Caroline Lornudd, Robert Lundmark, Rebecca Mosson, Henna Hasson
BACKGROUND: Leadership is a key feature in implementation efforts, which is highlighted in most implementation frameworks. However, in studying leadership and implementation, only few studies rely on established leadership theory, which makes it difficult to draw conclusions regarding what kinds of leadership managers should perform and under what circumstances. In industrial and organizational psychology, transformational leadership and contingent reward have been identified as effective leadership styles for facilitating change processes, and these styles map well onto the behaviors identified in implementation research...
2016: Implementation Science: IS
Stina Söderlund, Torsten Dahlén, Fredrik Sandin, Ulla Olsson-Strömberg, Maria Creignou, Arta Dreimane, Anna Lübking, Berit Markevärn, Anders Själander, Hans Wadenvik, Leif Stenke, Johan Richter, Martin Höglund
OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment. METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases...
July 18, 2016: European Journal of Haematology
Rose Lou Marie C Agbay, Nitin Jain, Sanam Loghavi, L Jeffrey Medeiros, Joseph D Khoury
Although generally considered a clinically indolent neoplasm, CLL/SLL may undergo transformation to a clinically aggressive lymphoma. The most common form of transformation, to DLBCL, is also known as Richter syndrome. Transformation determines the course of the disease and is associated with unfavorable patient outcome. Precise detection of transformation and identification of predictive biomarkers and specific molecular pathways implicated in the pathobiology of transformation in CLL/SLL will enable personalized therapeutic approach and provide potential avenues for improving the clinical outcome of patients...
October 2016: American Journal of Hematology
Sreejesh Sreedharanunni, Narender Kumar, Alka Khadwal
We report a rare CD5 positive B cell acute lymphoblastic leukemia (B-ALL) with a review of the clinopathological features and prognosis of previously reported cases in the literature. The aberrant expression of CD 5 antigen is uncommon in B-ALL; the morphological differential diagnosis includes blastic mantle cell lymphoma, denovo CD5(+) diffuse large B cell lymphoma and secondary diffuse large cell lymphoma/Richter's transformation. CD5(+) B cell ALL is commonly reported in younger patients (<18 years)...
June 2016: Indian Journal of Hematology & Blood Transfusion
Pavel Klener, Eva Fronkova, Adela Berkova, Radek Jaksa, Halka Lhotska, Kristina Forsterova, Jan Soukup, Vojtech Kulvait, Jarmila Vargova, Karel Fiser, Dana Prukova, Mahmudul Alam, Bokang Calvin Lenyeletse Maswabi, Kyra Michalova, Zuzana Zemanova, Tereza Jancuskova, Sona Pekova, Marek Trneny
Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-based second-line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole-exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of ATM gene or emergence of TP53, CREBBP, NUP214, FUBP1 and SF3B1 gene mutations...
November 15, 2016: International Journal of Cancer. Journal International du Cancer
Gianluigi Reda, Ramona Cassin, Sonia Fabris, Gabriella Ciceri, Bruno Fattizzo, Mariarita Sciumè, Nicola Orofino, Umberto Gianelli, Antonino Neri, Agostino Cortelezzi
Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia in a high-grade lymphoma usually presenting nodal and bone marrow involvement. Richter syndrome can be localized at extranodal sites including the gastrointestinal tract, lungs, and skin. Cutaneous RS is an extremely rare disease apparently showing a less aggressive course than common presentations. While nodal RS has been extensively investigated in literature, pathogenesis and prognosis of cutaneous RS are still partially unknown, even if a role of Epstein-Barr virus infection and p53 disruption has been suggested...
July 12, 2016: Hematological Oncology
Nitin Jain, Michael J Keating
INTRODUCTION: Richter transformation (RT) represents an aggressive transformation of chronic lymphocytic leukemia (CLL), most commonly into diffuse large B cell lymphoma (DLBCL). It occurs in around 5% of patients with CLL. AREA COVERED: This review will focus on the biology and treatment of RT. We also address the management of RT in the era of targeted therapies. Based on clonal relationship of large cell component to CLL, 2 distinct subtypes could be identified: clonally-related RT which carries a worse outcome, and clonally-unrelated RT where the outcomes are similar to de novo DLBCL...
August 2016: Expert Review of Hematology
Elizabeth J Soilleux, Andrew Wotherspoon, Toby A Eyre, Ruth Clifford, Maite Cabes, Anna H Schuh
AIMS: Richter's syndrome refers to high grade transformation of B-cell chronic lymphocytic leukaemia (CLL), usually to diffuse large B-cell lymphoma (DLBCL), as assessed by strict World Health Organisation (WHO)-defined histological criteria. Although a relatively evidence-poor area, the recommended clinical management of high grade transformation differs considerably from relapsed CLL. The 'CHOP-OR' trial was a single arm, multi-centre, non-randomised phase II NCRI trial in patients with newly diagnosed Richter's syndrome, recruiting from across the UK from April 2011 to December 2014...
June 27, 2016: Histopathology
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