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Treatment Plasma cell leukemia

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https://www.readbyqxmd.com/read/29773602/clofarabine-high-dose-cytarabine-and-liposomal-daunorubicin-in-pediatric-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-study
#1
Natasha K A van Eijkelenburg, Mareike Rasche, Essam Ghazaly, Michael N Dworzak, Thomas Klingebiel, Claudia Rossig, Guy Leverger, Jan Stary, Eveline S J M de Bont, Dana A Chitu, Yves Bertrand, Benoit Brethon, Brigitte Strahm, Inge M van der Sluis, Gertjan J L Kaspers, Dirk Reinhardt, C Michel Zwaan
Survival in children with relapsed/refractory acute myeloid leukemia is unsatisfactory. Treatment consists of one course fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase 2 dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose-levels of clofarabine (20-40mg/m2/day x5days) and liposomal daunorubicin (40-0mg/m2/day) were administered with cytarabine (2g/m2/day x5days)...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29768231/enhanced-stability-of-l-asparaginase-by-its-bioconjugation-to-poly-styrene-co-maleic-acid-and-ecoflex-nanoparticles
#2
Jaleh Varshosaz, Negin Anvari
Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L-asparaginase (L-ASNase) is one of the first drugs used in ALL treatment. Anti-tumor activity of L-ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L-ASNase polymer bioconjugate to improve pharmacokinetic, increase half-life and stability of the enzyme. The conjugations were achieved by the cross-linking agent of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29740433/syk-inhibition-induces-apoptosis-in-germinal-center-like-b-cells-by-modulating-the-antiapoptotic-protein-myeloid-cell-leukemia-1-affecting-b-cell-activation-and-antibody-production
#3
Nathalie Roders, Florence Herr, Gorbatchev Ambroise, Olivier Thaunat, Alain Portier, Aimé Vazquez, Antoine Durrbach
B cells play a major role in the antibody-mediated rejection (AMR) of solid organ transplants, a major public health concern. The germinal center (GC) is involved in the generation of donor-specific antibody-producing plasma cells and memory B cells, which are often poorly controlled by current treatments. Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the B-cell lymphoma-2 family, is essential for maintenance of the GC reaction and B-cell differentiation. During chronic AMR (cAMR), tertiary lymphoid structures resembling GCs appear in the rejected organ, suggesting local lymphoid neogenesis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29724147/characteristics-of-fibrinolytic-disorders-in-acute-promyelocytic-leukemia
#4
Ping Wang, Yingmei Zhang, Huiyuan Yang, Wenyi Hou, Bo Jin, Jinxiao Hou, Haitao Li, Hongli Zhao, Jin Zhou
OBJECTIVES: Catastrophic hemorrhage remains the main cause of acute promyelocytic leukemia (APL) treatment failure. This study was aimed to study the pathogenesis of coagulopathy in patients with APL. METHODS: Multiple procoagulant and profibrinolytic parameters in plasma and peripheral leukocytes from 24 patients with newly diagnosed APL accompanied by coagulopathy before and after arsenic trioxide (ATO) treatment were evaluated. RESULTS: Prior to the treatment, the patients had elevated D-dimer and decreased fibrinogen levels...
May 4, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29723984/triorganotin-derivatives-induce-cell-death-effects-on-l1210-leukemia-cells-at-submicromolar-concentrations-independently-of-p-glycoprotein-expression
#5
Viera Bohacova, Mario Seres, Lucia Pavlikova, Szilvia Kontar, Martin Cagala, Pavel Bobal, Jan Otevrel, Julius Brtko, Zdena Sulova, Albert Breier
The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR...
May 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29615003/role-of-cytarabine-in-paediatric-acute-promyelocytic-leukemia-treated-with-the-combination-of-all-trans-retinoic-acid-and-arsenic-trioxide-a-randomized-controlled-trial
#6
Li Zhang, Yao Zou, Yumei Chen, Ye Guo, Wenyu Yang, Xiaojuan Chen, Shuchun Wang, Xiaoming Liu, Min Ruan, Jiayuan Zhang, Tianfeng Liu, Fang Liu, Benquan Qi, Wenbin An, Yuanyuan Ren, Lixian Chang, Xiaofan Zhu
BACKGROUND: The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. METHODS: We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016...
April 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29608741/critically-elevated-potassium-in-a-55-year-old-female-with-chronic-lymphocytic-leukemia
#7
Jing Cao, Amy B Karger
Hyperkalemia in specimens from patients with chronic lymphocytic leukemia (CLL) may be due to tumor lysis syndrome (TLS) or specimen processing. This report describes a 55-year-old Caucasian woman with CLL who presented to an outside hospital with hyperkalemia and was transferred to a second hospital. Initial evaluation on the core laboratory chemistry analyzer (the VITROS 5600) and the ABL90 FLEX blood gas analyzer showed markedly elevated levels of potassium (K+). TLS was subsequently diagnosed, and dialysis was initiated...
March 28, 2018: Laboratory Medicine
https://www.readbyqxmd.com/read/29580262/treatment-of-b-cell-precursor-acute-lymphoblastic-leukemia-with-the-galectin-1-inhibitor-ptx008
#8
Helicia Paz, Eun Ji Joo, Chih-Hsing Chou, Fei Fei, Kevin H Mayo, Hisham Abdel-Azim, Haike Ghazarian, John Groffen, Nora Heisterkamp
BACKGROUND: Drug resistance of B-cell precursor acute lymphoblastic leukemia (BP-ALL) cells is conferred by both intrinsic and extrinsic factors, which could be targeted to promote chemo-sensitization. Our previous studies showed that Galectin-3, a lectin that clusters galactose-modified glycoproteins and that has both an intracellular and extracellular location, protects different subtypes of BP-ALL cells against chemotherapy. Galectin-1 is related to Galectin-3 and its expression was previously reported to be restricted to the MLL subtype of BP-ALL...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29550241/low-bioavailability-and-high-immunogenicity-of-a-new-brand-of-e-colil-asparaginase-with-active-host-contaminating-proteins
#9
Priscila Pini Zenatti, Natacha Azussa Migita, Nathália Moreno Cury, Rosângela Aparecida Mendes-Silva, Fabio Cesar Gozzo, Pedro Otavio de Campos-Lima, José Andrés Yunes, Silvia Regina Brandalise
The drug l-asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). The native E. colil-asparaginase used in Brazil until recently has been manufactured by Medac/Kyowa. Then a decision was taken by the Ministry of Health in 2017 to supply the National Health System with a cheaper alternative l-asparaginase manufactured by Beijing SL Pharmaceutical, called Leuginase®. As opposed to Medac, the asparaginase that has been in use in Brazil under the trade name of Aginasa®, it was not possible to find a single entry with the terms Leuginase in the Pubmed repository...
March 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29544089/effect-of-high-vegf-c-mrna-expression-on-achievement-of-complete-remission-in-adult-acute-myeloid-leukemia
#10
Sung-Eun Lee, Ji Yoon Lee, A-Reum Han, Hee-Sun Hwang, Woo-Sung Min, Hee-Je Kim
Although vascular endothelial growth factor-C (VEGF-C) is known to be expressed in acute myeloid leukemia (AML) blasts, the relevance of VEGF-C in the clinical setting remains to be fully explored. We examined the effect of VEGF-C on achievement of complete remission (CR) in adult de novo AML and immune cell population profiles according to VEGF-C mRNA expression. In comparison of VEGF-C expression between the no-CR and CR groups, the CR group showed a trend toward higher levels of plasma VEGF-C (P = .088), whereas mRNA expression of VEGF-C was downregulated (P = ...
March 12, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29513759/subtype-assignment-of-cll-based-on-b-cell-subset-associated-gene-signatures-from-normal-bone-marrow-a-proof-of-concept-study
#11
Caroline Holm Nørgaard, Lasse Hjort Jakobsen, Andrew J Gentles, Karen Dybkær, Tarec Christoffer El-Galaly, Julie Støve Bødker, Alexander Schmitz, Preben Johansen, Tobias Herold, Karsten Spiekermann, Jennifer R Brown, Josephine L Klitgaard, Hans Erik Johnsen, Martin Bøgsted
Diagnostic and prognostic evaluation of chronic lymphocytic leukemia (CLL) involves blood cell counts, immunophenotyping, IgVH mutation status, and cytogenetic analyses. We generated B-cell associated gene-signatures (BAGS) based on six naturally occurring B-cell subsets within normal bone marrow. Our hypothesis is that by segregating CLL according to BAGS, we can identify subtypes with prognostic implications in support of pathogenetic value of BAGS. Microarray-based gene-expression samples from eight independent CLL cohorts (1,024 untreated patients) were BAGS-stratified into pre-BI, pre-BII, immature, naïve, memory, or plasma cell subtypes; the majority falling within the memory (24...
2018: PloS One
https://www.readbyqxmd.com/read/29504446/the-clinical-significance-of-b-cell-maturation-antigen-as-a-therapeutic-target-and-biomarker
#12
Eric Sanchez, Edward J Tanenbaum, Saurabh Patil, Mingjie Li, Camilia M Soof, Aleksandra Vidisheva, Gabriel N Waterman, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James Berenson
B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients...
April 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29501828/primary-plasma-cell-leukemia-in-the-era-of-novel-agents-for-myeloma-a-multicenter-retrospective-analysis-of-outcome
#13
Chezi Ganzel, Ory Rouvio, Irit Avivi, Hila Magen, Osnat Jarchowsky, Katrin Herzog, Yossi Cohen, Tamar Tadmor, Netanel A Horwitz, Merav Leiba, Arnon Nagler, Yael Cohen, Shlomo Bulvik, Aaron Polliack, Jacob M Rowe, Moshe E Gatt
Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma with a dismal prognosis. This retrospective multi-center study examines the national experience of PPCL in the era of novel agents. During 2002-2016, thirty-nine patients with PPCL were identified in 11 Israeli centers. One-fifth of them died in the first 2 months after diagnosis. The overall survival (OS) of those who survived the first 3 months was 22.5 months. About 70% of patients received at least one type of immunomodulatory drug (IMiD) and similarly proteasome inhibitor (PI) during treatment...
May 2018: Leukemia Research
https://www.readbyqxmd.com/read/29494851/enhanced-perforin-expression-associated-with-dasatinib-therapy-in-natural-killer-cells
#14
Noriyoshi Iriyama, Hiromichi Takahashi, Katsuhiro Miura, Yoshihito Uchino, Masaru Nakagawa, Yoshihiro Hatta, Masami Takei
We investigated the effects of dasatinib on natural killer (NK) cell-induced signaling protein and perforin expression as well as plasma cytokine levels by analyzing blood samples from patients with well-controlled chronic myeloid leukemia receiving tyrosine kinase inhibitor (TKI) therapy. Perforin expression and phosphorylation of signal transducer and activator of transcription (STAT) 1, STAT3, Janus kinase (JAK) 1, and JAK2 in NK cells were evaluated by flow cytometry, and the levels of plasma cytokines, including interferon (IFN)-γ and interleukin (IL)-2, were determined by enzyme-linked immunosorbent assays in 40 patients (dasatinib, n = 23; imatinib, n = 11; and nilotinib, n = 6)...
May 2018: Leukemia Research
https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#15
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with 89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29353760/targeting-the-il-17-il-6-axis-can-alter-growth-of-chronic-lymphocytic-leukemia-in-vivo-in-vitro
#16
Fang Zhu, Lindsay McCaw, David E Spaner, Reginald M Gorczynski
The tumor microenvironment (TME) is critical to the longevity of tumor B cells in chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs) and the cytokines they produce including IL-6 are important components of the TME in CLL. We found BMMSCs supported the survival of CLL cells in vitro through an IL-6 dependent mechanism. IL-17 which induces IL-6 generation in a variety of cells increased production of IL-6 both in CLL cells and BMMSCs in vitro. In a xenograft CLL mouse model, BMMSCs and the culture supernatant of BMMSCs increased engraftment of CLL cells through an IL-6 mediated mechanism with human recombinant IL-6 showing similar effects in vivo...
March 2018: Leukemia Research
https://www.readbyqxmd.com/read/29339551/inhibition-of-flt3-and-pim-kinases-by-ec-70124-exerts-potent-activity-in-preclinical-models-of-acute-myeloid-leukemia
#17
Noelia Puente-Moncada, Paula Costales, Isaac Antolín, Luz Elena Núñez, Patricia Oro, Maria Ana Hermosilla, Jhudit Perez-Escuredo, Nicolas Rios-Lombardia, Ana M Sanchez-Sanchez, Elisa Luño, Carmen Rodriguez, Vanesa Martin, Francisco Moris
Internal tandem duplication (ITD) or tyrosine kinase domain mutations of FLT3 is the most frequent genetic alteration in acute myeloid leukemia (AML) and are associated with poor disease outcome. Despite considerable efforts to develop single-target FLT3 drugs, so far, the most promising clinical response has been achieved using the multikinase inhibitor midostaurin. Here we explore the activity of the indolocarbazole EC-70124, from the same chemical space as midostaurin, in preclinical models of AML, focusing on those bearing FLT3-ITD mutations...
January 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29333561/pharmacokinetics-of-the-b-cell-lymphoma-2-bcl-2-inhibitor-venetoclax-in-female-subjects-with-systemic-lupus-erythematosus
#18
Mukul Minocha, Jiewei Zeng, Jeroen K Medema, Ahmed A Othman
BACKGROUND AND OBJECTIVE: Venetoclax is an oral selective Bcl-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia with 17p deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax for the treatment of systemic lupus erythematosus (SLE). This work characterized the pharmacokinetics of venetoclax in female subjects with SLE. METHODS: Single (10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching placebo were evaluated using randomized, double-blind, placebo-controlled designs (6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom enrolled twice)...
January 15, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29332353/aesculetin-6-7-dihydroxycoumarin-exhibits-potent-and-selective-antitumor-activity-in-human-acute-myeloid-leukemia-cells-thp-1-via-induction-of-mitochondrial-mediated-apoptosis-and-cancer-cell-migration-inhibition
#19
Jian Gong, Wei-Guo Zhang, Xiao-Fen Feng, Mei-Juan Shao, Chao Xing
PURPOSE: The main target of the present research was to examine the antitumor properties of aesculetin in human acute myeloid leukemia cancer cells (THP-1) and peripheral blood mono-nucleated cells (PBMCs) (used as normal cell line model) along with the determination of its effects on induction of apoptosis, inhibition of cancer cell migration and changes in Bcl-2/Bax protein expressions. METHODS: MTT colorimetric bioassay was performed to study the impact of this natural compound on cytotoxicity of both cell types...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29217783/somatic-stat3-mutations-in-felty-syndrome-an-implication-for-a-common-pathogenesis-with-large-granular-lymphocyte-leukemia
#20
Paula Savola, Oscar Brück, Thomas Olson, Tiina Kelkka, Markku J Kauppi, Panu E Kovanen, Soili Kytölä, Tuulikki Sokka-Isler, Thomas P Loughran, Marjatta Leirisalo-Repo, Satu Mustjoki
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities...
February 2018: Haematologica
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