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chronic lymphocytic leukaemia

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https://www.readbyqxmd.com/read/28220479/a-phase-1-2-trial-of-ublituximab-a-novel-anti-cd20-monoclonal-antibody-in-patients-with-b-cell-non-hodgkin-lymphoma-or-chronic-lymphocytic-leukaemia-previously-exposed-to-rituximab
#1
Ahmed Sawas, Charles M Farber, Marshall T Schreeder, Mazen Y Khalil, Daruka Mahadevan, Changchun Deng, Jennifer E Amengual, Petros G Nikolinakos, Jill M Kolesar, John G Kuhn, Peter Sportelli, Hari P Miskin, Owen A O'Connor
This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#2
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28208230/emerging-role-of-gsk-3%C3%AE-in-the-pathobiology-of-classical-hodgkin-lymphoma
#3
Claudio Agostinelli, Silvia Carloni, Francesco Limarzi, Simona Righi, Maria Antonella Laginestra, Gerardo Musuraca, Michelangelo Fiorentino, Roberta Napolitano, Antonio Cuneo, Daniele Vergara, Pier Luigi Zinzani, Sabattini Elena, Stefano A Pileri, Serena De Matteis
AIMS: GSK-3β is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, metabolism, survival and cellular senescence. Its main biological function is to inhibit β-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway, however GSK-3β interacts with multiple signaling pathways and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3β in classical Hodgkin Lymphomas (cHL)...
February 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28199309/phosphatidylinositol-3-kinase-%C3%AE-blockade-increases-genomic-instability-in-b-cells
#4
Mara Compagno, Qi Wang, Chiara Pighi, Taek-Chin Cheong, Fei-Long Meng, Teresa Poggio, Leng-Siew Yeap, Elif Karaca, Rafael B Blasco, Fernanda Langellotto, Chiara Ambrogio, Claudia Voena, Adrian Wiestner, Siddha N Kasar, Jennifer R Brown, Jing Sun, Catherine J Wu, Monica Gostissa, Frederick W Alt, Roberto Chiarle
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28179635/chronic-lymphocytic-leukaemia
#5
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
No abstract text is available yet for this article.
February 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28166664/-tp53-mutation-analysis-in-chronic-lymphocytic-leukaemia
#6
Viktória Fésüs, Dóra Marosvári, Béla Kajtár, Péter Attila Király, Judit Demeter, Tímea Gurbity Pálfi, Miklós Egyed, Márk Plander, Péter Farkas, Zoltán Mátrai, András Matolcsy, Csaba Bödör
INTRODUCTION: In recent years much progress has been made in the therapy of chronic lymphocytic leukaemia, as the new innovative medicine proved to be effective in managing patients carrying TP53 abnormalities. To identify all these patients, it is essential to screen for both forms of TP53 defects, including both 17p deletions and TP53 mutations. AIM: The aim of this study was to determine the frequency of TP53 mutations and their association with 17p deletions in a large Hungarian cohort of 196 patients suffering from chronic lymphocytic leukaemia...
February 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28165464/genome-wide-association-analysis-implicates-dysregulation-of-immunity-genes-in-chronic-lymphocytic-leukaemia
#7
Philip J Law, Sonja I Berndt, Helen E Speedy, Nicola J Camp, Georgina P Sava, Christine F Skibola, Amy Holroyd, Vijai Joseph, Nicola J Sunter, Alexandra Nieters, Silvia Bea, Alain Monnereau, David Martin-Garcia, Lynn R Goldin, Guillem Clot, Lauren R Teras, Inés Quintela, Brenda M Birmann, Sandrine Jayne, Wendy Cozen, Aneela Majid, Karin E Smedby, Qing Lan, Claire Dearden, Angela R Brooks-Wilson, Andrew G Hall, Mark P Purdue, Tryfonia Mainou-Fowler, Claire M Vajdic, Graham H Jackson, Pierluigi Cocco, Helen Marr, Yawei Zhang, Tongzhang Zheng, Graham G Giles, Charles Lawrence, Timothy G Call, Mark Liebow, Mads Melbye, Bengt Glimelius, Larry Mansouri, Martha Glenn, Karen Curtin, W Ryan Diver, Brian K Link, Lucia Conde, Paige M Bracci, Elizabeth A Holly, Rebecca D Jackson, Lesley F Tinker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Marc Maynadie, James McKay, Demetrius Albanes, Stephanie Weinstein, Zhaoming Wang, Neil E Caporaso, Lindsay M Morton, Richard K Severson, Elio Riboli, Paolo Vineis, Roel C H Vermeulen, Melissa C Southey, Roger L Milne, Jacqueline Clavel, Sabine Topka, John J Spinelli, Peter Kraft, Maria Grazia Ennas, Geoffrey Summerfield, Giovanni M Ferri, Robert J Harris, Lucia Miligi, Andrew R Pettitt, Kari E North, David J Allsup, Joseph F Fraumeni, James R Bailey, Kenneth Offit, Guy Pratt, Henrik Hjalgrim, Chris Pepper, Stephen J Chanock, Chris Fegan, Richard Rosenquist, Silvia de Sanjose, Angel Carracedo, Martin J S Dyer, Daniel Catovsky, Elias Campo, James R Cerhan, James M Allan, Nathanial Rothman, Richard Houlston, Susan Slager
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10(-13)), 1q42.13 (rs41271473, P=1.06 × 10(-10)), 4q24 (rs71597109, P=1.37 × 10(-10)), 4q35.1 (rs57214277, P=3...
February 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28154156/lung-consolidation-responding-to-chemotherapy
#8
Prasanth Balasubramaniam, Ram V Nampoothiri, Nalini Gupta, Pankaj Malhotra
Consolidations in the pulmonary parenchyma are mostly infective, although they can rarely be due to autoimmune and neoplastic processes. Consolidations, especially in the setting of underlying immunosuppressive haematological malignancy, are usually presumed infective by the treating physician. Pulmonary involvement in chronic lymphocytic leukaemia presenting as consolidations and type 1 respiratory failure, responding to systemic chemotherapy, is a rare and uncommon presentation.
February 2, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28139406/another-treatment-option-for-relapsed-or-refractory-chronic-lymphocytic-leukaemia
#9
Francesca R Mauro
No abstract text is available yet for this article.
January 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28139405/idelalisib-or-placebo-in-combination-with-bendamustine-and-rituximab-in-patients-with-relapsed-or-refractory-chronic-lymphocytic-leukaemia-interim-results-from-a-phase-3-randomised-double-blind-placebo-controlled-trial
#10
Andrew D Zelenetz, Jacqueline C Barrientos, Jennifer R Brown, Bertrand Coiffier, Julio Delgado, Miklós Egyed, Paolo Ghia, Árpád Illés, Wojciech Jurczak, Paula Marlton, Marco Montillo, Franck Morschhauser, Alexander S Pristupa, Tadeusz Robak, Jeff P Sharman, David Simpson, Lukáš Smolej, Eugen Tausch, Adeboye H Adewoye, Lyndah K Dreiling, Yeonhee Kim, Stephan Stilgenbauer, Peter Hillmen
BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled...
January 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28130034/nice-guidance-on-ibrutinib-for-previously-treated-chronic-lymphocytic-leukaemia-and-untreated-chronic-lymphocytic-leukaemia-in-the-presence-of-17p-deletion-or-tp53-mutation
#11
Boglarka Mikudina, Melinda Goodall, Amanda I Adler
No abstract text is available yet for this article.
January 24, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28112199/genome-wide-association-analysis-of-chronic-lymphocytic-leukaemia-hodgkin-lymphoma-and-multiple-myeloma-identifies-pleiotropic-risk-loci
#12
Philip J Law, Amit Sud, Jonathan S Mitchell, Marc Henrion, Giulia Orlando, Oleg Lenive, Peter Broderick, Helen E Speedy, David C Johnson, Martin Kaiser, Niels Weinhold, Rosie Cooke, Nicola J Sunter, Graham H Jackson, Geoffrey Summerfield, Robert J Harris, Andrew R Pettitt, David J Allsup, Jonathan Carmichael, James R Bailey, Guy Pratt, Thahira Rahman, Chris Pepper, Chris Fegan, Elke Pogge von Strandmann, Andreas Engert, Asta Försti, Bowang Chen, Miguel Inacio da Silva Filho, Hauke Thomsen, Per Hoffmann, Markus M Noethen, Lewin Eisele, Karl-Heinz Jöckel, James M Allan, Anthony J Swerdlow, Hartmut Goldschmidt, Daniel Catovsky, Gareth J Morgan, Kari Hemminki, Richard S Houlston
B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105602/ibrutinib-a-review-in-chronic-lymphocytic-leukaemia
#13
Emma D Deeks
Ibrutinib (Imbruvica(®)) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...
February 2017: Drugs
https://www.readbyqxmd.com/read/28102226/chronic-lymphocytic-leukaemia
#14
REVIEW
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all...
19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28102205/chronic-lymphocytic-leukaemia
#15
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28089635/venetoclax-plus-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-a-phase-1b-study
#16
John F Seymour, Shuo Ma, Danielle M Brander, Michael Y Choi, Jacqueline Barrientos, Matthew S Davids, Mary Ann Anderson, Anne W Beaven, Steven T Rosen, Constantine S Tam, Betty Prine, Suresh K Agarwal, Wijith Munasinghe, Ming Zhu, L Leanne Lash, Monali Desai, Elisa Cerri, Maria Verdugo, Su Young Kim, Rod A Humerickhouse, Gary B Gordon, Thomas J Kipps, Andrew W Roberts
BACKGROUND: Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. METHODS: Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial...
February 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28089631/chronic-lymphocytic-leukaemia-a-step-ahead-in-the-journey-toward-eradication
#17
Lorenzo De Paoli, Gianluca Gaidano
No abstract text is available yet for this article.
January 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28089238/ruxolitinib-for-symptom-control-in-patients-with-chronic-lymphocytic-leukaemia-a-single-group-phase-2-trial
#18
Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov
BACKGROUND: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis...
February 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28072473/pharmacokinetics-of-obinutuzumab-in-chinese-patients-with-b-cell-lymphomas
#19
John Zhai, Yan Qin, Jun Zhu, Yuqin Song, Zhixiang Shen, Xin Du, Candice Jamois, Michael Brewster, Yuankai Shi, Jun Shi
AIM: The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients. METHODS: GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China...
January 10, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#20
Harvey E Johnston, Matthew J Carter, Kerry L Cox, Melanie Dunscombe, Antigoni Manousopoulou, Paul A Townsend, Spiro D Garbis, Mark S Cragg
Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukaemia (CLL), are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumour, frequently affecting children, whilst CLL typically presents as an indolent, slow-progressing leukaemia affecting the elderly. The B-cell-specific over-expression of the myc and tcl1 oncogenes in mice induce spontaneous malignancies modelling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labelling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumours...
January 4, 2017: Molecular & Cellular Proteomics: MCP
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