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Treatment Plasma cell leukemia

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https://www.readbyqxmd.com/read/28530540/novel-n-mustard-benzimidazoles-benzothiazoles-hybrids-synthesis-and-anticancer-evaluation
#1
Dilip P Detroja, Tai-Lin Chen, Yi-Wen Lin, Tsai-Yi Yen, Ming-Hsi Wu, Tung-Hu Tsai, Krunal Maheriya, Rajesh Kakadiya, Te-Chang Lee, Anamik Shah, Tsann-Long Su
BACKGROUND: Bendamustine, an N-mustard-benzoimidazole hybrid conjugate, was recently approved for the treatment of chronic lymphocytic leukemia. However, the short half-life of bendamustine may limit its clinical applications. OBJECTIVE: The purpose of this study is to design and synthesize compounds with a more favorable pharmacokinetic profile. METHODS: We synthesized a series of hybrid molecules comprising a phenyl N-mustard moiety and benzothiazole or benzimidazole scaffold linked via an ureido linker and evaluated their antitumor activity and plasma stability...
May 22, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#2
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28504647/identification-of-a-nucleoside-analog-active-against-adenosine-kinase-expressing-plasma-cell-malignancies
#3
Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J Barelli, Michelle A Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H Shoemaker, J David Warren, Olivier Elemento, Kenneth M Kaye, Ethel Cesarman
Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28485366/plasma-cell-leukemia-single-institution-experience
#4
K Govind Babu, Linu Abraham Jacob, Ankit Agarwal, K C Lakshmaiah, D Lokanatha, M C Suresh Babu, L K Rajeev, K N Lokesh, A H Rudresha
BACKGROUND: The first case of plasma cell leukemia (PCL) was recognized by Gluzinski and Reichentein. It is the most aggressive among the monoclonal gammopathies. It is diagnosed by the presence of more than 20% plasma cells in the peripheral blood or an absolute plasma cell count of> 2000/mm3. Because of the relatively low incidence, most data come from case reports and retrospective studies. No prospective series have been published, and only seven reports including more than twenty patients have been identified...
October 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28454312/treatment-with-a-selenium-platinum-compound-induced-t-cell-acute-lymphoblastic-leukemia-lymphoma-cells-apoptosis-through-the-mitochondrial-signaling-pathway
#5
Feifei Wu, Wei Cao, Huaping Xu, Mingxia Zhu, Jing Wang, Xiaoyan Ke
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive hematological disorder that is sensitive to chemotherapy; however, it exhibits frequent relapse rates. Platinum-containing therapeutics are the first-line salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium-containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer properties have been poorly investigated. In the present study, the Cell Counting Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt on cell viability...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28442922/inhibition-of-pcsk9-protects-against-radiation-induced-damage-of-prostate-cancer-cells
#6
Si-Shun Gan, Jian-Qing Ye, Lei Wang, Fa-Jun Qu, Chuan-Min Chu, Yi-Jun Tian, Wei Yang, Xin-Gang Cui
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein expressed primarily in the liver, formerly known to maintain plasma lipid homeostasis by regulating low-density lipoprotein receptor levels, and its exact role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to investigate the function of PCSK9 in the radioresistance of PCa cells. METHODS: PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by transient transfection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28423727/paclitaxel-synergizes-with-exposure-time-adjusted-cd22-targeting-immunotoxins-against-b-cell-malignancies
#7
Fabian Müller, Stephanie Stookey, Tyler Cunningham, Ira Pastan
CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL) patients. The goal was to enhance rIT efficacy in vivo and to define a strong combination treatment. Activity of Moxetumomab pasudotox (Moxe) and LR combined with paclitaxel was tested against MCL cell lines in vitro and as bolus doses or continuous infusion in xenograft models. In the KOPN-8 ALL xenograft, Moxe or paclitaxel alone was active, but all mice died from leukemia; when combined, 60% of the mice achieved a sustained complete remission...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#8
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#9
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28403213/m-copa-suppresses-endolysosomal-kit-akt-oncogenic-signalling-through-inhibiting-the-secretory-pathway-in-neoplastic-mast-cells
#10
Yasushi Hara, Yuuki Obata, Keita Horikawa, Yasutaka Tasaki, Kyohei Suzuki, Takatsugu Murata, Isamu Shiina, Ryo Abe
Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28337541/tyrosine-kinase-inhibitor-therapy-induced-changes-in-humoral-immunity-in-patients-with-chronic-myeloid-leukemia
#11
Hanna L M Rajala, Mohamed El Missiry, Anniina Ruusila, Perttu Koskenvesa, Tim H Brümmendorf, Bjorn T Gjertsen, Jeroen Janssen, Kourosh Lotfi, Berit Markevärn, Ulla Olsson-Strömberg, Leif Stenke, Jesper Stentoft, Johan Richter, Henrik Hjorth-Hansen, Anna Kreutzman, Satu Mustjoki
PURPOSE: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. METHODS: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment...
March 23, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28325251/interferon-induced-thrombotic-microangiopathy-tma-analysis-and-concise-review
#12
REVIEW
Ajay Kundra, Jen Chin Wang
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28321034/galectin-9-as-a-predictive-marker-for-the-onset-of-immune-related-adverse-effects-associated-with-anti-ccr4-moab-therapy-in-patients-with-adult-t-cell-leukemia
#13
Tareg Omer Mohammed, Haorile Chagan-Yasutan, Yugo Ashino, Wakana Nakayama, Yayoi Takahashi, Taizo Shimomura, Tetsuhiro Fujimoto, Yuko Watanabe, Toshiro Niki, Hitoshi Suzushima, Toshio Hattori
Adult T-cell leukemia/lymphoma (ATL/ATLL) is one of the most malignant lymphomas with poor prognosis. ATL/ATLL cells express CC chemokine receptor 4, and mogamulizumab (anti-CCR4 monoclonal antibody) exhibits strong cytotoxicity for ATL/ATLL cells. We analyzed plasma samples of 6 patients with ATL/ATLL treated with chemotherapy followed by mogamulizumab therapy (mogatherapy) for changes in the levels of biomarkers in relation to immune-related adverse effects. As treatment is often associated with skin eruptions, we investigated the profiles of inflammatory cytokines, including galectin-9 (Gal-9), which becomes increased in various infectious diseases and allergic patients...
March 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28303902/ms4a4a-a-novel-cell-surface-marker-for-m2-macrophages-and-plasma-cells
#14
Ratna Sanyal, Maria J Polyak, Jonathan Zuccolo, Mandip Puri, Lili Deng, Luc Roberts, Ania Zuba, Jan Storek, Joanne M Luider, Ellen M Sundberg, Adnan Mansoor, Eva Baigorri, Michael P Chu, Andrew R Belch, Linda M Pilarski, Julie P Deans
MS4A4A is a member of the membrane-spanning, 4 domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcRβ (MS4A2) and Htm4 (MS4A3). Like the first three members of this family, transcription of MS4A4A appears to be limited to hematopoietic cells. To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets we generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood we found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes...
March 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28288853/establishing-evidence-based-thresholds-and-laboratory-practices-to-reduce-inappropriate-treatment-of-pseudohyperkalemia
#15
Pratistha Ranjitkar, Dina N Greene, Geoffrey S Baird, Andrew N Hoofnagle, Patrick C Mathias
BACKGROUND: Unrecognized pseudohyperkalemia (PHK), defined as an artificial increase in measured potassium concentration, due to thrombocytosis and leukocytosis can lead to inappropriate patient treatment. Understanding the laboratory and patient characteristics that increase risk of PHK is key to preventing diagnostic errors. METHODS: Serum/plasma potassium results collected at 2 laboratories over 4years were selected based on blood cell counts collected within 24h and whole blood potassium concentrations determined within 2h of the serum/plasma sample...
March 10, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28283735/in-vitro-and-in-vivo-evaluation-of-dasatinib-and-imatinib-on-physiological-parameters-of-pulmonary-arterial-hypertension
#16
Bethany Baumgart, Mausumee Guha, James Hennan, Julia Li, Jochen Woicke, Damir Simic, Michael Graziano, Nicola Wallis, Thomas Sanderson, Roderick Todd Bunch
PURPOSE: Pulmonary arterial hypertension (PAH) results from occlusion or vasoconstriction of pulmonary vessels, leading to progressive right ventricular failure. Dasatinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukemia, has been associated with PAH. In contrast, the BCR-ABL1 TKI imatinib has demonstrated anti-vasoproliferative properties and has been investigated as a potential treatment for PAH. Here we describe studies evaluating the effects of dasatinib and imatinib on cardiovascular and pulmonary functions to understand the reported differential consequences of the two TKIs in a clinical setting...
March 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28270565/midostaurin-a-novel-protein-kinase-inhibitor-for-the-treatment-of-acute-myelogenous-leukemia-insights-from-human-absorption-metabolism-and-excretion-studies-of-a-bddcs-ii-drug
#17
Handan He, Phi Tran, Helen Gu, Vivienne Tedesco, Jin Zhang, Wen Lin, Ewa Gatlik, Kai Klein, Tycho Heimbach
The absorption, metabolism, and excretion of midostaurin, a potent class III tyrosine protein kinase inhibitor for acute myelogenous leukemia, were evaluated in healthy subjects. A microemulsion formulation was chosen to optimize absorption. After a 50-mg [(14)C]midostaurin dose, oral absorption was high (>90%) and relatively rapid. In plasma, the major circulating components were midostaurin (22%), CGP52421 (32.7%), and CGP62221 (27.7%). Long plasma half-lives were observed for midostaurin (20.3 hours), CGP52421 (495 hours), and CGP62221 (33...
May 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28240053/plasma-matrix-metalloprotease-9-correlates-with-blood-lymphocytosis-leukemic-cell-invasiveness-and-prognosis-in-b-cell-chronic-lymphocytic-leukemia
#18
Milena Gusella, Caterina Bolzonella, Rossella Paolini, Elisabetta Rodella, Laura Bertolaso, Cinzia Scipioni, Silvia Bellini, Antonio Cuneo, Felice Pasini, Emilio Ramazzina
The complex biology underlying chronic lymphocytic leukemia cell migration and tissue invasiveness is not yet completely understood and might provide novel predictive markers and therapeutic targets. A total of 36 patients out of treatment from at least 3 months were enrolled and followed up for a median period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue inhibitor of metalloproteases 1 plasma levels and production/release from lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay (ELISA) analysis...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28186131/recq1-helicase-is-involved-in-replication-stress-survival-and-drug-resistance-in-multiple-myeloma
#19
E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here, we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28179997/the-plant-defensin-nad1-induces-tumor-cell-death-via-a-non-apoptotic-membranolytic-process
#20
Amy A Baxter, Ivan Kh Poon, Mark D Hulett
Cationic anti-microbial peptides (CAPs) have an important role in host innate defense against pathogens such as bacteria and fungi. Many CAPs including defensins also exhibit selective cytotoxic activity towards mammalian cells via both apoptotic and non-apoptotic processes, and are being investigated as potential anticancer agents. The anti-fungal plant defensin from ornamental tobacco, Nicotiana alata Defensin 1 (NaD1), was recently shown to induce necrotic-like cell death in a number of tumor cell types within 30 min of treatment, at a concentration of 10 μM...
2017: Cell Death Discovery
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