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Leukemia, lymphoma, multiple myeloma

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https://www.readbyqxmd.com/read/28053195/tcr-based-therapy-for-multiple-myeloma-and-other-b-cell-malignancies-targeting-intracellular-transcription-factor-bob1
#1
Lorenz Jahn, Pleun Hombrink, Renate S Hagedoorn, Michel G D Kester, Dirk M van der Steen, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, Arnoud H de Ru, Marjolein P Schoonakker, Miranda H Meeuwsen, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28018601/the-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-hematologic-malignancies-multiple-myeloma-lymphoma-and-acute-leukemia
#2
Michael Boyiadzis, Michael R Bishop, Rafat Abonour, Kenneth C Anderson, Stephen M Ansell, David Avigan, Lisa Barbarotta, Austin John Barrett, Koen Van Besien, P Leif Bergsagel, Ivan Borrello, Joshua Brody, Jill Brufsky, Mitchell Cairo, Ajai Chari, Adam Cohen, Jorge Cortes, Stephen J Forman, Jonathan W Friedberg, Ephraim J Fuchs, Steven D Gore, Sundar Jagannath, Brad S Kahl, Justin Kline, James N Kochenderfer, Larry W Kwak, Ronald Levy, Marcos de Lima, Mark R Litzow, Anuj Mahindra, Jeffrey Miller, Nikhil C Munshi, Robert Z Orlowski, John M Pagel, David L Porter, Stephen J Russell, Karl Schwartz, Margaret A Shipp, David Siegel, Richard M Stone, Martin S Tallman, John M Timmerman, Frits Van Rhee, Edmund K Waller, Ann Welsh, Michael Werner, Peter H Wiernik, Madhav V Dhodapkar
Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27941287/adoptive-immunotherapy-utilizing-anti-cd19-chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#3
Iekuni Oh, Yukiko Oh, Ken Ohmine
Genetically modified T-cells with forced expression of anti-CD19 chimeric antigen receptor (CD19 CAR) have demonstrated promising clinical results for relapsed and refractory B cell malignancies in early clinical trial settings. The first beneficial tumor regressions were identified among approximately half of CLL patients in 2011. Similarly, CD19 CAR T-cells achieved remissions in about 80% of aggressive B-cell lymphomas in 2012. Furthermore, in 2013 this cellular therapy showed an extremely high rate of efficacy against refractory CD19 positive acute lymphoid leukemia, which had been regarded as the most difficult to treat hematologic disease...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27924815/the-relationship-between-eligibility-criteria-and-adverse-events-in-randomized-controlled-trials-of-hematologic-malignancies
#4
A Statler, T Radivoyevitch, C Siebenaller, A T Gerds, M Kalaycio, E Kodish, S Mukherjee, C Cheng, M A Sekeres
To minimize adverse events unrelated to drugs and maximize the likelihood of drug approvals, eligibility criteria for randomized controlled trials (RCTs) may be overly restrictive. The purpose of this study was to determine if RCTs in hematologic malignancies exclude patients irrespective of known toxicities or observed adverse events (AEs). MEDLINE was searched from 1/2010 to 1/2015 for RCTs published in high-impact journals. Of 97 trials, 33% were conducted in leukemia, 28% in lymphoma, 34% in multiple myeloma, and 5% in myelodysplastic syndromes or myelofibrosis...
December 7, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27914102/examining-temporal-effects-on-cancer-risk-in-the-international-nuclear-workers-study-inworks
#5
Robert D Daniels, Stephen J Bertke, David B Richardson, Elisabeth Cardis, Michael Gillies, Jacqueline A O'Hagan, Richard Haylock, Dominique Laurier, Klervi Leuraud, Monika Moissonnier, Isabelle Thierry-Chef, Ausrele Kesminiene, Mary K Schubauer-Berigan
The paper continues the series of publications from the International Nuclear Workers Study cohort (INWORKS) that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure...
December 3, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#6
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#7
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#8
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90%C3%A2-rasgrp1-and-hsp90%C3%A2-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#9
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here, we show that trichostatin A, romidepsin and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen-activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
December 16, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#10
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#11
REVIEW
Alessandro Allegra, Vanessa Innao, Demetrio Gerace, Doriana Vaddinelli, Caterina Musolino
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors...
November 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27784345/-changes-of-adamts13-activity-and-tsp1-level-in-patients-with-hematologic-malignancies
#12
Cai-Feng Sun, Xia Zhao, Fang Han, Qi Jia, Liang Wang, Guang Lu, Hui-Fang Ding
OBJECTIVE: To investigate the changes of thrombospondin 1(TSP1) level and von Willebrand factor cleaving protease(ADAMTS13) activity in the patients with hematologic malignancies before and after treatment and to evaluate their clinical significance. METHODS: Eighty-two patients with hematologic malignancies were enrolled in this study, among them 20 patients were with acute leukemia, 48 patients were with lymphoma and 14 patients were with multiple myeloma. The plasma samples of 82 patients with hematologic malignancies and 45 healthy controls were collected...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27761889/microrna-155-in-serum-derived-extracellular-vesicles-as-a-potential-biomarker-for-hematologic-malignancies-a-short-report
#13
Antonella Caivano, Francesco La Rocca, Vittorio Simeon, Marco Girasole, Simone Dinarelli, Ilaria Laurenzana, Angelo De Stradis, Luciana De Luca, Stefania Trino, Antonio Traficante, Giovanni D'Arena, Giovanna Mansueto, Oreste Villani, Giuseppe Pietrantuono, Luca Laurenti, Luigi Del Vecchio, Pellegrino Musto
PURPOSE: The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported...
October 19, 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27760111/the-mcl1-inhibitor-s63845-is-tolerable-and-effective-in-diverse-cancer-models
#14
András Kotschy, Zoltán Szlavik, James Murray, James Davidson, Ana Leticia Maragno, Gaëtane Le Toumelin-Braizat, Maïa Chanrion, Gemma L Kelly, Jia-Nan Gong, Donia M Moujalled, Alain Bruno, Márton Csekei, Attila Paczal, Zoltán B Szabo, Szabolcs Sipos, Gábor Radics, Agnes Proszenyak, Balázs Balint, Levente Ondi, Gábor Blasko, Alan Robertson, Allan Surgenor, Pawel Dokurno, Ijen Chen, Natalia Matassova, Julia Smith, Christopher Pedder, Christopher Graham, Aurélie Studeny, Gaëlle Lysiak-Auvity, Anne-Marie Girard, Fabienne Gravé, David Segal, Chris D Riffkin, Giovanna Pomilio, Laura C A Galbraith, Brandon J Aubrey, Margs S Brennan, Marco J Herold, Catherine Chang, Ghislaine Guasconi, Nicolas Cauquil, Fabien Melchiore, Nolwen Guigal-Stephan, Brian Lockhart, Frédéric Colland, John A Hickman, Andrew W Roberts, David C S Huang, Andrew H Wei, Andreas Strasser, Guillaume Lessene, Olivier Geneste
Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway...
October 27, 2016: Nature
https://www.readbyqxmd.com/read/27756310/phase-specific-and-lifetime-costs-of-cancer-care-in-ontario-canada
#15
Claire de Oliveira, Reka Pataky, Karen E Bremner, Jagadish Rangrej, Kelvin K W Chan, Winson Y Cheung, Jeffrey S Hoch, Stuart Peacock, Murray D Krahn
BACKGROUND: Cancer is a major public health issue and represents a significant economic burden to health care systems worldwide. The objective of this analysis was to estimate phase-specific, 5-year and lifetime net costs for the 21 most prevalent cancer sites, and remaining tumour sites combined, in Ontario, Canada. METHODS: We selected all adult patients diagnosed with a primary cancer between 1997 and 2007, with valid ICD-O site and histology codes, and who survived 30 days or more after diagnosis, from the Ontario Cancer Registry (N = 394,092)...
October 18, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27729803/bet-inhibitors-in-the-treatment-of-hematologic-malignancies-current-insights-and-future-prospects
#16
Sameem M Abedin, Craig S Boddy, Hidayatullah G Munshi
The bromodomain and extra-terminal (BET) family of proteins are important epigenetic regulators involved in promoting gene expression of critical oncogenes. BET inhibitors have been demonstrated to repress c-Myc expression, and were initially shown to have efficacy in a number of c-Myc-dependent hematologic malignancies. Recent studies have now revealed a broader role for BET inhibitors in hematologic malignancies. In this review, we summarize the efficacy of BET inhibitors in preclinical models of acute leukemia, lymphoma, and multiple myeloma...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27631245/hiv-and-cancer-registry-linkage-identifies-a-substantial-burden-of-cancers-in-persons-with-hiv-in-india
#17
Sheela V Godbole, Karabi Nandy, Mansi Gauniyal, Pallavi Nalawade, Suvarna Sane, Shravani Koyande, Joy Toyama, Asha Hegde, Phil Virgo, Kishor Bhatia, Ramesh S Paranjape, Arun R Risbud, Sam M Mbulaiteye, Ronald T Mitsuyasu
We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27631102/radiation-risks-of-leukemia-lymphoma-and-multiple-myeloma-incidence-in-the-mayak-cohort-1948-2004
#18
Irina S Kuznetsova, Elena V Labutina, Nezahat Hunter
Incidence of all types of lymphatic and hematopoietic cancers, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, acute and chronic myeloid leukemia (AML and CML respectively), chronic lymphocytic leukemia (CLL) and other forms of leukemia have been studied in a cohort of 22,373 workers employed at the Mayak Production Association (PA) main facilities during 536,126 person-years of follow-up from the start of employment between 1948 and 1982 to the end of 2004. Risk assessment was performed for both external gamma-radiation and internal alpha-exposure of red bone marrow due to incorporated Pu-239 using Mayak Workers Dosimetry System 2008 taking into account non-radiation factors...
2016: PloS One
https://www.readbyqxmd.com/read/27623550/facile-synthesis-and-18-f-radiolabeling-of-%C3%AE-4%C3%AE-1-specific-llp2a-aryltrifluoroborate-peptidomimetic-conjugates
#19
Daniel Walker, Ying Li, Áron Roxin, Paul Schaffer, Michael J Adam, David M Perrin
The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1 integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence, (111)In-SPECT, and (64)Cu- and (68)Ga-PET imaging. Despite these successes, to date there is no report of an (18)F-labeled LLP2A conjugate. Notably, fluorine-18 is a preferred radionuclide for PET imaging, yet its short half-life and general inactivity under aqueous conditions present challenges for peptide labeling...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27595249/-nosocomial-pneumonia-in-patients-with-haematological-malignancies
#20
Lucía Martínez-Hernández, Diana Vilar-Compte, Patricia Cornejo-Juárez, Patricia Volkow-Fernández
INTRODUCTION: Nosocomial pneumonia (NP) in patients with hematological malignancies (HM) has an attributable mortality over 90%. There are few studies that report the incidence of nosocomial infections in patients with HM. OBJECTIVE: To describe the epidemiology and clinical course of NP in a cohort of patients with hematologic malignancies. MATERIAL AND METHODS: Single-center study of patients with leukemia, lymphoma or multiple myeloma diagnosed with NP, hospitalized between January 2011 and December 2012...
July 2016: Gaceta Médica de México
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