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Treatment Plasma cell leukemia

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https://www.readbyqxmd.com/read/28760306/high-risk-multiple-myeloma-definition-and-management
#1
REVIEW
Nisha S Joseph, Silvia Gentili, Jonathan L Kaufman, Sagar Lonial, Ajay K Nooka
The prognosis of patients with multiple myeloma has significantly improved after the introduction of novel concepts of immunomodulation and proteasome inhibition in myeloma therapies. In conjunction with the use of high-dose therapy and autologous stem cell transplantation, these newer antimyeloma agents facilitated the augmentation of deeper responses and as a result, enhanced survival outcomes. Despite mounting clinical evidence that novel therapies may mitigate the poor prognostic impact of some predictors historically considered "harbingers of doom" in myeloma such as t(4;14), the benefit of these advances is less evident in patients who present with genetically defined high-risk features such as presence of chromosomal abnormalities del17p, t(14;16), or t(14;20), or among patients presenting with plasma cell leukemia...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28744022/granulocyte-colony-stimulating-factor-gcsf-fused-with-fc-domain-produced-from-e-coli-is-less-effective-than-polyethylene-glycol-conjugated-gcsf
#2
Bich Hang Do, Hyo Jeong Kang, Jung-A Song, Minh Tan Nguyen, Sangsu Park, Jiwon Yoo, Anh Ngoc Nguyen, Grace G Kwon, Jaepyeong Jang, Mihee Jang, Sunju Lee, Seoungjun So, Seongrak Sim, Kyung Jin Lee, Mark J Osborn, Han Choe
Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28711674/hplc-hg-afs-determination-of-arsenic-species-in-acute-promyelocytic-leukemia-apl-plasma-and-blood-cells
#3
Meihua Guo, Wenjing Wang, Xin Hai, Jin Zhou
Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO3H2O2 and analyzed by HG-AFS...
July 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28702160/bk-virus-associated-hemorrhagic-cystitis-in-patients-with-allogeneic-hematopoietic-cell-transplantation-report-of-three-cases
#4
Duygu Mert, Hikmetullah Batgi, Alparslan Merdin, Sabahat Çeken, Mehmet Sinan Dal, Emre Tekgündüz, Fevzi Altuntaş, Mustafa Ertek
BK viras is a human polyoma viras. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28674892/surface-profiling-of-extracellular-vesicles-from-plasma-or-ascites-fluid-using-dotscan-antibody-microarrays
#5
Larissa Belov, Susannah Hallal, Kieran Matic, Jerry Zhou, Sandra Wissmueller, Nuzhat Ahmed, Sumaiya Tanjil, Stephen P Mulligan, O Giles Best, Richard J Simpson, Richard I Christopherson
DotScan antibody microarrays were initially developed for the extensive surface profiling of live leukemia and lymphoma cells. DotScan's diagnostic capability was validated with an extensive clinical trial using mononuclear cells from the blood or bone marrow of leukemia or lymphoma patients. DotScan has also been used for the profiling of surface proteins on peripheral blood mononuclear cells (PBMC) from patients with HIV, liver disease, and stable and progressive B-cell chronic lymphocytic leukemia (CLL)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28668490/co-infections-by-double-stranded-dna-viruses-after-ex-vivo-t-cell-depleted-cd34-selected-hematopoietic-cell-transplantation
#6
Yao-Ting Huang, Seong Jin Kim, Yeon Joo Lee, Daniel Burack, Paige Nichols, Molly Maloy, Miguel-Angel Perales, Sergio A Giralt, Ann A Jakubowski, Genovefa A Papanicolaou
Recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) are at risk of infection by double-stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV). Healthcare utilization in the first 6 months post-HCT was compared between patients with dsDNA viremia versus no viremia...
June 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#7
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28634317/the-role-of-frontline-autologous-stem-cell-transplantation-for-primary-plasma-cell-leukemia-a-retrospective-multicenter-study-kmm160
#8
Sung-Hoon Jung, Je-Jung Lee, Kihyun Kim, Cheolwon Suh, Dok Hyun Yoon, Chang-Ki Min, Sang Kyun Sohn, Chul Won Choi, Ho Sup Lee, Hyo Jung Kim, Ho-Jin Shin, Soo-Mee Bang, Sung-Soo Yoon, Seong Kyu Park, Ho-Young Yhim, Min Kyoung Kim, Jae-Cheol Jo, Yeung-Chul Mun, Jae Hoon Lee, Jin Seok Kim
Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620566/leukemia-cutis-associated-with-secondary-plasma-cell-leukemia
#9
Nicole C DeMartinis, Megan M Brown, Brian R Hinds, Philip R Cohen
Plasma cell leukemia is an uncommon, aggressive variant of leukemia that may occur de novo or in association with multiple myeloma. Leukemia cutis is the cutaneous manifestation of leukemia, and indicates an infiltration of the skin by malignant leukocytes or their precursors. Plasma cell leukemia cutis is a rare clinical presentation of leukemia. We present a man who developed plasma cell leukemia cutis in association with multiple myeloma. Cutaneous nodules developed on his arms and legs 50 days following an autologous stem cell transplant...
May 9, 2017: Curēus
https://www.readbyqxmd.com/read/28619847/targeted-activation-of-the-shp-1-pp2a-signaling-axis-elicits-apoptosis-of-chronic-lymphocytic-leukemia-cells
#10
Elena Tibaldi, Mario Angelo Pagano, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Valeria Pavan, Luciana Bordin, Andrea Visentin, Francesca Zonta, Gianpietro Semenzato, Anna Maria Brunati, Livio Trentin
Lyn, a member of the Src family of kinases, is a key factor in the dysregulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and serine/threonine phosphatase 2A, eventually triggering apoptosis...
August 2017: Haematologica
https://www.readbyqxmd.com/read/28599273/targeting-bcr-abl-stem-progenitor-cells-and-bcr-abl-t315i-mutant-cells-by-effective-inhibition-of-the-bcr-abl-tyr177-grb2-complex
#11
Min Chen, Ali G Turhan, Hongxia Ding, Qingcong Lin, Kun Meng, Xiaoyan Jiang
Treatment of BCR-ABL+ human leukemia has been significantly improved by ABL tyrosine kinase inhibitors (TKIs), but they are not curative for most patients and relapses are frequently associated with BCR-ABL mutations, warranting new targets for improved treatments. We have now demonstrated that protein expression of human estrogen receptor alpha 36 (ERα36), an alternative splicing variant of human estrogen receptor alpha 66 (ERα66), is highly increased in TKI-insensitive CD34+ chronic myeloid leukemia (CML) cells and BCR-ABL-T315I mutant cells, and is abnormally localized in plasma membrane and cytoplasm...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596939/undifferentiated-pleomorphic-sarcoma-and-the-importance-of-considering-the-oncogenic-and-immune-suppressant-role-of-the-human-t-cell-lymphotropic-virus-type-1-a-case-report
#12
Sergio Lupo, Carolina Berini, Camila Cánepa, Eduardo Santini Araujo, Mirna Biglione
INTRODUCTION: Soft-tissue sarcomas account for 0.7% of all malignant tumors, with an incidence rate of 3 per 100,000 persons/year. The undifferentiated pleomorphic sarcoma (UPS) with giant cells, a high grade tumor of soft tissue, is very unusual, especially in young adults before the age of 40. Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus, classified as group 1 human carcinogens by The International Agency for Research on Cancer, that causes an aggressive malignancy known as adult T-cell lymphoma/leukemia and a progressive chronic inflammatory neurological disease named HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28562380/pharmacokinetics-of-venetoclax-in-patients-with-17p-deletion-chronic-lymphocytic-leukemia
#13
Ahmed Hamed Salem, Martin Dunbar, Suresh K Agarwal
Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28561902/safety-and-pharmacokinetics-of-bendamustine-rapid-infusion-formulation
#14
Eric M Cheung, William J Edenfield, Bassam Mattar, Stephen P Anthony, Peter J Mutch, Brian Chanas, Mark Smith, Adrian Hepner
Bendamustine hydrochloride (BDM) is approved in the United States to treat chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin lymphoma. The first formulation marketed in the United States (original BDM) was a lyophilized product requiring reconstitution prior to dilution to the final admixture. A liquid formulation of BDM was subsequently introduced that did not require reconstitution before dilution. Both formulations are administered as a 500 mL admixture with a recommended infusion time of 30 or 60 minutes for chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma, respectively...
May 31, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28555083/ppar-delta-modulates-membrane-cholesterol-and-cytokine-signaling-in-malignant-b-cells
#15
L Sun, Y Shi, G Wang, X Wang, S Zeng, S E Dunn, G D Fairn, Y-J Li, D E Spaner
New treatment strategies may be uncovered with a deeper understanding of the mechanisms that underlie aberrant signal transduction in B cell cancers such as chronic lymphocytic leukemia (CLL). The lipid-activated nuclear receptor peroxisome proliferator-activated receptor delta (PPARδ) mediates a number of features of aggressive cancers and was found to enhance janus kinase (JAK)-mediated phosphorylation of signal transducer and activator of transcription (STAT) proteins in B lymphoma cell-lines and primary CLL cells...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28544116/incidence-characteristics-and-outcome-of-solitary-plasmacytoma-and-plasma-cell-leukemia-population-based-data-from-the-swedish-myeloma-register
#16
Hareth Nahi, Anna Genell, Göran Wålinder, Katarina Uttervall, Gunnar Juliusson, Karin Forsberg, Markus Hansson, Ronald Svensson, Olle Linder, Kristina Carlson, Bo Björkstrand, Sigurdur Y Kristinsson, Ulf Henrik Mellqvist, Cecilie Blimark, Ingemar Turesson
Solitary plasmacytoma (SP) and Plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP), (n=124) and extramedullary plasmacytoma (EMP), (n=67) have better overall survival (OS) than MM (n=3549)...
May 22, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28530540/novel-n-mustard-benzimidazoles-benzothiazoles-hybrids-synthesis-and-anticancer-evaluation
#17
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
#18
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
#19
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...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28485366/plasma-cell-leukemia-single-institution-experience
#20
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
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