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John Byrd

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https://www.readbyqxmd.com/read/28299881/the-regulation-of-tumor-suppressive-microrna-mir-126-in%C3%A2-chronic-lymphocytic-leukemia
#1
Daphne Guinn, Amy Lehman, Catherine Fabian, Lianbo Yu, Kami Maddocks, Leslie A Andritsos, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Jennifer A Woyach, John C Byrd, Amy J Johnson
The introduction of miR profiling of chronic lymphocytic leukemia (CLL) patients with different cytogenetic profiles and responses to therapy has allowed incorporation of important miR-mRNA interactions into the understanding of disease biology. In this study, we performed miR expression analysis using NanoString nCounter to discover differentially regulated miRs after therapy with the Bruton tyrosine kinase inhibitor ibrutinib. Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy...
March 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28275031/nccn-guidelines-insights-chronic-lymphocytic-leukemia-small-lymphocytic-leukemia-version-1-2017
#2
William G Wierda, Andrew D Zelenetz, Leo I Gordon, Jeremy S Abramson, Ranjana H Advani, C Babis Andreadis, Nancy Bartlett, John C Byrd, Paolo Caimi, Luis E Fayad, Richard I Fisher, Martha J Glenn, Thomas M Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T Hoppe, Steven M Horwitz, Mark S Kaminski, Christopher R Kelsey, Youn H Kim, Susan Krivacic, Ann S LaCasce, Michael G Martin, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A Saad, Erin D Snyder, Lubomir Sokol, Lode J Swinnen, Julie M Vose, Joachim Yahalom, Mary A Dwyer, Hema Sundar
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28270022/a-phase-1-trial-of-the-hdac-inhibitor-ar-42-in-patients-with-multiple-myeloma-and-t-and-b-cell-lymphomas
#3
Douglas W Sborov, Alessandro Canella, Erinn M Hade, Xiaokui Mo, Soun Khountham, Jiang Wang, Wenjun Ni, Ming Poi, Christopher Coss, Zhongfa Liu, Mitch A Phelps, Amir Mortazavi, Leslie Andritsos, Robert A Baiocchi, Beth A Christian, Don M Benson, Joseph Flynn, Pierluigi Porcu, John C Byrd, Flavia Pichiorri, Craig C Hofmeister
Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40 mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively...
March 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28213868/elliptical-fourier-analysis-fundamentals-applications-and-value-for-forensic-anthropology
#4
REVIEW
Jodi Caple, John Byrd, Carl N Stephan
The numerical description of skeletal morphology enables forensic anthropologists to conduct objective, reproducible, and structured tests, with the added capability of verifying morphoscopic-based analyses. One technique that permits comprehensive quantification of outline shape is elliptical Fourier analysis. This curve fitting technique allows a form's outline to be approximated via the sum of multiple sine and cosine waves, permitting the profile perimeter of an object to be described in a dense (continuous) manner at a user-defined level of precision...
February 17, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28183528/transethnic-genome-wide-scan-identifies-novel-alzheimer-s-disease-loci
#5
Gyungah R Jun, Jaeyoon Chung, Jesse Mez, Robert Barber, Gary W Beecham, David A Bennett, Joseph D Buxbaum, Goldie S Byrd, Minerva M Carrasquillo, Paul K Crane, Carlos Cruchaga, Philip De Jager, Nilufer Ertekin-Taner, Denis Evans, M Danielle Fallin, Tatiana M Foroud, Robert P Friedland, Alison M Goate, Neill R Graff-Radford, Hugh Hendrie, Kathleen S Hall, Kara L Hamilton-Nelson, Rivka Inzelberg, M Ilyas Kamboh, John S K Kauwe, Walter A Kukull, Brian W Kunkle, Ryozo Kuwano, Eric B Larson, Mark W Logue, Jennifer J Manly, Eden R Martin, Thomas J Montine, Shubhabrata Mukherjee, Adam Naj, Eric M Reiman, Christiane Reitz, Richard Sherva, Peter H St George-Hyslop, Timothy Thornton, Steven G Younkin, Badri N Vardarajan, Li-San Wang, Jens R Wendlund, Ashley R Winslow, Jonathan Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard Schellenberg, Kathryn L Lunetta, Lindsay A Farrer
INTRODUCTION: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. METHODS: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset...
February 7, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28104811/correction-in-vivo-ncl-targeting-affects-breast-cancer-aggressiveness-through-mirna-regulation
#6
Flavia Pichiorri, Dario Palmieri, Luciana De Luca, Jessica Consiglio, Jia You, Alberto Rocci, Tiffany Talabere, Claudia Piovan, Alessandro Lagana, Luciano Cascione, Jingwen Guan, Pierluigi Gasparini, Veronica Balatti, Gerard Nuovo, Vincenzo Coppola, Craig C Hofmeister, Guido Marcucci, John C Byrd, Stefano Volinia, Charles L Shapiro, Michael A Freitas, Carlo M Croce
No abstract text is available yet for this article.
January 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28099078/prevalence-of-terrapene-herpesvirus-1-in-free-ranging-eastern-box-turtles-terrapene-carolina-carolina-in-tennessee-and-illinois
#7
Lauren P Kane, Matthew C Allender, Grace Archer, Elena Dzhaman, John Pauley, A Russell Moore, Marilyn O Ruiz, Rebecca L Smith, John Byrd, Christopher A Phillips
Diseases affecting the upper respiratory tract, such as herpesviruses, are well described in captive chelonians worldwide, but their importance in free-ranging populations is less well known. To characterize the disease epidemiology of terrapene herpesvirus 1 (TerHV1), 409 free-ranging eastern box turtles ( Terrapene carolina carolina) in Tennessee and Illinois were tested for TerHV1 in 2013 and 2014 using TaqMan quantitative PCR. Whole blood and swabs of the oral mucosa were collected from 365 adults (154 females, 195 males, 16 unknown sex) and 44 juveniles...
January 18, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28073846/extended-treatment-with-single-agent-ibrutinib-at-the-420-mg-dose-leads-to-durable-responses-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#8
Steven E Coutré, Richard R Furman, Ian W Flinn, Jan A Burger, Kristie Blum, Jeff Sharman, Jeffrey Jones, William Wierda, Weiqiang Zhao, Nyla A Heerema, Amy J Johnson, Anh Tran, Cathy Zhou, Elizabeth Bilotti, Danelle F James, John C Byrd, Susan O'Brien
Purpose: Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase Ib/II study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28008612/a-large-sample-test-of-a-semi-automated-clavicle-search-engine-to-assist-skeletal-identification-by-radiograph-comparison
#9
Susan S D'Alonzo, Pierre Guyomarc'h, John E Byrd, Carl N Stephan
In 2014, a morphometric capability to search chest radiograph databases by quantified clavicle shape was published to assist skeletal identification. Here, we extend the validation tests conducted by increasing the search universe 18-fold, from 409 to 7361 individuals to determine whether there is any associated decrease in performance under these more challenging circumstances. The number of trials and analysts were also increased, respectively, from 17 to 30 skeletons, and two to four examiners. Elliptical Fourier analysis was conducted on clavicles from each skeleton by each analyst (shadowgrams trimmed from scratch in every instance) and compared to the search universe...
January 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/27977057/randomized-phase-2-study-of-otlertuzumab-and-bendamustine-versus-bendamustine-in-patients-with-relapsed-chronic-lymphocytic-leukaemia
#10
Tadeusz Robak, Andrzej Hellmann, Janusz Kloczko, Javier Loscertales, Ewa Lech-Maranda, John M Pagel, Anthony Mato, John C Byrd, Farrukh T Awan, Holger Hebart, Jose A Garcia-Marco, Brian T Hill, Michael Hallek, Amy J Eisenfeld, Scott C Stromatt, Ulrich Jaeger
Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m(2) ) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone...
February 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27903679/the-bruton-s-tyrosine-kinase-btk-inhibitor-acalabrutinib-demonstrates-potent-on-target-effects-and-efficacy-in-two-mouse-models-of-chronic-lymphocytic-leukemia
#11
Sarah E M Herman, Arnau Montraveta, Carsten U Niemann, Helena Mora-Jensen, Michael Gulrajani, Fanny Krantz, Rose Mantel, Lisa L Smith, Fabienne McClanahan, Bonnie Harrington, Dolors Colomer, Todd Covey, John C Byrd, Raquel Izumi, Allard Kaptein, Roger Ulrich, Amy Johnson, Brian J Lannutti, Adrian Wiestner, Jennifer A Woyach
PURPOSE: Acalabrutinib (ACP-196) is a novel, potent, and highly selective BTK inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the anti-tumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL). EXPERIMENTAL DESIGN: Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG primary CLL xenograft model...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27892987/sweet-like-eruption-associated-with-obinutuzumab-therapy-for-chronic-lymphocytic-leukemia
#12
Abraham M Korman, Justin G Hastings, John C Byrd, Benjamin H Kaffenberger
No abstract text is available yet for this article.
January 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/27853650/therapeutic-cd94-nkg2a-blockade-improves-natural-killer-cell-dysfunction-in-chronic-lymphocytic-leukemia
#13
Emily M McWilliams, Jennifer M Mele, Carolyn Cheney, Elizabeth A Timmerman, Faraz Fiazuddin, Ethan J Strattan, Xiaokui Mo, John C Byrd, Natarajan Muthusamy, Farrukh T Awan
Natural killer (NK)-cell count is predictive of chronic lymphoid leukemia (CLL) disease progression and their dysfunction is well documented, but the etiology of this is currently lacking. CLL cells have been shown to over-express HLA-E, the natural ligand for NKG2A expressed on NK-cells that generates a distinct negative signal relative to direct NK-cell cytotoxicity in other disease models. Utilizing a novel anti-NKG2A monoclonal blocking antibody (mAb), monalizumab, we explored the in vitro preclinical activity of targeting the NKG2A receptor, and the NKG2A/HLA-E interaction as a mechanism of tumor evasion in CLL patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27852036/interim-analysis-of-a-phase-i-iia-trial-assessing-e39-gm-csf-a-folate-binding-protein-vaccine-to-prevent-recurrence-in-ovarian-and-endometrial-cancer-patients
#14
Doreen O Jackson, Kevin Byrd, Timothy J Vreeland, Diane F Hale, Garth S Herbert, Julia M Greene, Erika J Schneble, John S Berry, Alfred F Trappey, G T Clifton, Mark O Hardin, Jonathan Martin, John C Elkas, Thomas P Conrads, Kathleen M Darcy, Chad A Hamilton, George L Maxwell, George E Peoples
BACKGROUND: Folate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date. METHODS: HLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG)...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27802969/ibrutinib-efficacy-and-tolerability-in-patients-with-relapsed-chronic-lymphocytic-leukemia-following-allogeneic-hct
#15
Christine E Ryan, Bita Sahaf, Aaron C Logan, Susan O'Brien, John C Byrd, Peter Hillmen, Jennifer R Brown, Martin J S Dyer, Anthony R Mato, Michael J Keating, Samantha Jaglowski, Fong Clow, Andrew R Rezvani, Lori Styles, Steven E Coutre, David B Miklos
Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton's tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87...
December 22, 2016: Blood
https://www.readbyqxmd.com/read/27784745/mutational-landscape-and-gene-expression-patterns-in-adult-acute-myeloid-leukemias-with-monosomy-7-as-a-sole-abnormality
#16
Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Stefano Volinia, James S Blachly, Deedra Nicolet, Christopher Oakes, Karl Kroll, Shelley Orwick, Andrew J Carroll, Richard M Stone, John C Byrd, Albert de la Chapelle, Clara D Bloomfield
Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data...
January 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27780867/interferon-%C3%AE-promotes-antibody-mediated-fratricide-of-acute-myeloid-leukemia-cells
#17
Kavin Fatehchand, Elizabeth L McMichael, Brenda F Reader, Huiqing Fang, Ramasamy Santhanam, Shalini Gautam, Saranya Elavazhagan, Payal Mehta, Nathaniel J Buteyn, Giovanna Merchand-Reyes, Sumithira Vasu, Xiaokui Mo, Don M Benson, James S Blachly, William E Carson, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid lineage blasts. Due to its heterogeneity and to the high rate of acquired drug resistance and relapse, new treatment strategies are needed. Here, we demonstrate that IFNγ promotes AML blasts to act as effector cells within the context of antibody therapy. Treatment with IFNγ drove AML blasts toward a more differentiated state, wherein they showed increased expression of the M1-related markers HLA-DR and CD86, as well as of FcγRI, which mediates effector responses to therapeutic antibodies...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27775550/microrna-29b-mediates-altered-innate-immune-development-in-acute-leukemia
#18
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27766616/genomics-of-primary-chemoresistance-and-remission-induction-failure-in-paediatric-and-adult-acute-myeloid-leukaemia
#19
Fiona C Brown, Paolo Cifani, Esther Drill, Jie He, Eric Still, Shan Zhong, Sohail Balasubramanian, Dean Pavlick, Bahar Yilmazel, Kristina M Knapp, Todd A Alonzo, Soheil Meshinchi, Richard M Stone, Steven M Kornblau, Guido Marcucci, Alan S Gamis, John C Byrd, Mithat Gonen, Ross L Levine, Alex Kentsis
Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases...
January 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27760757/assessment-of-cd37-b-cell-antigen-and-cell-of-origin-significantly-improves-risk-prediction-in-diffuse-large-b-cell-lymphoma
#20
Zijun Y Xu-Monette, Ling Li, John C Byrd, Kausar J Jabbar, Ganiraju C Manyam, Charlotte Maria de Winde, Michiel van den Brand, Alexandar Tzankov, Carlo Visco, Jing Wang, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L Richards, Eric D Hsi, William W L Choi, Jooryung Huh, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Ben M Parsons, Jane N Winter, Michael Wang, Frederick B Hagemeister, Miguel A Piris, J Han van Krieken, L Jeffrey Medeiros, Yong Li, Annemiek B van Spriel, Ken H Young
CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37(-)) in ∼60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell-like (GCB)/activated B-cell-like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37(-), including TP53 mutation, NF-κB(high), Myc(high), phosphorylated STAT3(high), survivin(high), p63(-), and BCL6 translocation...
December 29, 2016: Blood
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