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Monoclonal gammopathy of undetermined significance

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https://www.readbyqxmd.com/read/28229908/multiple-myeloma-tumor-cells-are-selectively-killed-by-pharmacologically-dosed-ascorbic-acid
#1
Jiliang Xia, Hongwei Xu, Xiaoyan Zhang, Chantal Allamargot, Kristen L Coleman, Randy Nessler, Ivana Frech, Guido Tricot, Fenghuang Zhan
High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138(+) MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients...
February 16, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#2
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28182355/pure-red-cell-aplasia-associated-with-monoclonal-gammopathy-of-undetermined-significance-and-literature-review
#3
Hyunjung Gu, Woo-In Lee, You La Jeon, So Young Kang, Myeong Hee Kim, Tae Sung Park
BACKGROUND: Pure red cell aplasia (PRCA) is an uncommon disease which involves an almost complete absence of the erythroid lineage in bone marrow (BM) and causes severe anemia. Cases due to monoclonal gammopathy occurring in plasma cell disorder have been infrequently reported. Here we report a case of PRCA associated plasma cell disorder, especially monoclonal gammopathy of undetermined significance (MGUS). METHODS: A 55-year-old male visited the ER due to general weakness...
February 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28158311/a-single-arm-open-label-phase-2-clinical-trial-evaluating-disease-response-following-treatment-with-bi-505-a-human-anti-intercellular-adhesion-molecule-1-monoclonal-antibody-in-patients-with-smoldering-multiple-myeloma
#4
Stina Wichert, Gunnar Juliusson, Åsa Johansson, Elisabeth Sonesson, Ingrid Teige, Anna Teige Wickenberg, Björn Frendeus, Magnus Korsgren, Markus Hansson
BACKGROUND: Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects...
2017: PloS One
https://www.readbyqxmd.com/read/28122920/combined-traf6-targeting-and-proteasome-blockade-has-anti-tumor-and-anti-bone-resorptive-effects
#5
Haiming Chen, Mingjie Li, Eric Sanchez, Cathy S Wang, Tiffany Lee, Camilia M Soof, Christian E Casas, Jasmin Cao, Colin Xie, Kyle A Udd, Kevin DeCorso, George Y Tang, Tanya M Spektor, James R Berenson
: Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been implicated in polyubiquitin-mediated IL-1R/TLR signaling through activation of IκB kinase (IKK) to regulate the NF-κB and JNK signaling pathways. Here, TRAF6 protein was determined to be overexpressed in bone marrow mononuclear cells (BMMCs) from multiple myeloma (MM) patients. TRAF6 expression in BMMCs from patients with progressive disease is significantly elevated as compared to individuals in complete remission, with monoclonal gammopathy of undetermined significance, or healthy subjects...
January 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28116941/pomalidomide-experience-an-effective-therapeutic-approach-with-immunomodulatory-drugs-in-a-patient-with-relapsed-refractory-multiple-myeloma
#6
Concetta Conticello, Marina Parisi, Alessandra Romano, Valeria Calafiore, Flavia Ancora, Alessia La Fauci, Maria Letizia Consoli, Francesco Di Raimondo
Here we discuss the case of a heavily pretreated male patient with relapsed-refractory multiple myeloma and previous monoclonal gammopathy of undetermined significance who initiated a fifth-line treatment with pomalidomide (4 mg orally, days 1-21 of a 28-day cycle) and low-dose dexamethasone (40 mg weekly orally). A total of 3 months later, very good partial response was achieved and complete response was maintained for 7 months. This case illustrates the field-practice experience on the benefits of pomalidomide in a relapsed-refractory multiple myeloma patient with a previous history of monoclonal gammopathy of undetermined significance...
February 2017: Future Oncology
https://www.readbyqxmd.com/read/28088969/-the-clinical-features-of-patients-with-lymphoplasmacytic-diseases-harboring-myd88-l265p-mutation
#7
Y Ren, B Q Zhou, Y Xu, C C Fu, H J Shen, Z X Ding, D P Wu
Objective: To explore the clinical features of lymphoplasmacytic diseases with MyD88 L265P mutation. Methods: To analyze the distribution of MYD88 L265P mutation in patients with lymphoplasmacytic diseases by using of ARMS PCR-CE. Results: There were 25(30.9%) MyD88 L265P mutated patients in 81 patients. The mutation was frequently observed in 14 patients with WM (77.8%, 14/18), 2 patients with lymphoplasmacytic lymphoma (66.7%, 2/3), 1 acute lymphocytic leukemia patient (50.0%, 1/2), 3 multiple myeloma patients (30...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28070468/multiple-myeloma-associated-chronic-inflammatory-demyelinating-polyradiculoneuropathy-the-importance-of-continued-surveillance
#8
Adebayo A Fasanya, Michael F Loncharich, Viral Gandhi, Sandeep Rana, Marvin Balaan
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease presenting with weakness and numbness in a remitting or chronic progressive course. It is known to have several clinical presentations and several associated diseases. CIDP has been associated with multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), and other paraproteinemias. We present a case of refractory CIDP in which the initial workup for multiple myeloma was negative, and multiple myeloma was then diagnosed two and half years later...
November 28, 2016: Curēus
https://www.readbyqxmd.com/read/28061988/treatment-of-high-risk-smoldering-myeloma
#9
REVIEW
Neha Korde
Multiple myeloma (MM) is a hematologic malignancy of the plasma cell that causes symptoms of bone pain, renal failure, and anemia. It is usually preceded by a precursor disease state, such as smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), and traditional dogma dictates that treatment should be initiated on frank MM symptom development. Emerging evidence suggests that a defined group of "high-risk SMM" may benefit from early treatment, before organ damage and symptoms actually occur...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28050052/the-hematologic-definition-of-monoclonal-gammopathy-of-undetermined-significance-in-relation-to-paraproteinemic-keratopathy-an-american-ophthalmological-society-thesis
#10
Walter Lisch, Joanna Wasielica-Poslednik, Tero Kivelä, Ursula Schlötzer-Schrehardt, Jens M Rohrbach, Walter Sekundo, Uwe Pleyer, Christina Lisch, Alexander Desuki, Heidi Rossmann, Jayne S Weiss
PURPOSE: To determine if paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of undetermined significance (MGUS) causes distinct patterns of corneal opacification that can be distinguished from hereditary, immunologic, or inflammatory causes. METHODS: A retrospective, interventional study of patients showed distinct bilateral opacity patterns of the cornea at the eye clinics of Hanau, Mainz, Helsinki, Marburg, and Berlin between 1993 and 2015...
August 2016: Transactions of the American Ophthalmological Society
https://www.readbyqxmd.com/read/28040690/obesity-and-the-transformation-of-monoclonal-gammopathy-of-undetermined-significance-to-multiple-myeloma-a-population-based-cohort-study
#11
Su-Hsin Chang, Suhong Luo, Theodore S Thomas, Katiuscia K O'Brian, Graham A Colditz, Nils P Carlsson, Kenneth R Carson
BACKGROUND: Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). This study investigates the role of obesity in the progression of MGUS to MM. METHODS: A retrospective identified cohort of patients in the US Veterans Health Administration database diagnosed with MGUS between October 1, 1999, and December 31, 2009, was followed through August 6, 2013...
May 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28025584/genome-wide-association-study-of-immunoglobulin-light-chain-amyloidosis-in-three-patient-cohorts-comparison-to-myeloma
#12
M I da Silva Filho, A Försti, N Weinhold, I Mezian, C Campo, S Huhn, J Nickel, P Hoffmann, M M Nöthen, K-H Jöckel, S Landi, J S Mitchell, D Johnson, G J Morgan, R Houlston, H Goldschmidt, A Jauch, P Milani, G Merlini, D Rowcieno, P Hawkins, U Hegenbart, G Palladini, A Wechalekar, S O Schönland, K Hemminki
Immunoglobulin light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibers derived from immunoglobulin light chain. AL amyloidosis and multiple myeloma (MM) originate from monoclonal gammopathy of undetermined significance. We wanted to characterize germline susceptibility to AL amyloidosis using a genome-wide association study (GWAS) on 1229 AL amyloidosis patients from Germany, UK and Italy, and 7526 healthy local controls. For comparison with MM, recent GWAS data on 3790 cases were used...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27998645/thrombotic-microangiopathy-associated-with-monoclonal-gammopathy
#13
Aishwarya Ravindran, Ronald S Go, Fernando C Fervenza, Sanjeev Sethi
Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13...
December 17, 2016: Kidney International
https://www.readbyqxmd.com/read/27983725/a-gene-expression-inflammatory-signature-specifically-predicts-multiple-myeloma-evolution-and-patients-survival
#14
C Botta, M T Di Martino, D Ciliberto, M Cucè, P Correale, M Rossi, P Tagliaferri, P Tassone
Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution...
December 16, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27979847/concomitant-multiple-myeloma-gastric-adenocarcinoma-and-evan-s-syndrome-in-a-patient-presenting-with-anaemia
#15
Maged Al-Ammari, Soheir Adam
An association between multiple myeloma (MM) and solid tumours has been previously described.(1) Furthermore, autoimmune disorders can precede plasma cell dyscrasias, and the pathogenesis of MM maybe linked to chronic immune stimulation. (2) We describe a case of concomitant MM and gastric adenocarcinoma preceded by Evan's syndrome. A previously healthy woman presented to the emergency room with symptomatic anaemia. Her initial workup was compatible with autoimmune haemolytic anaemia and monoclonal gammopathy of undetermined significance...
December 15, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27974705/are-neurological-complications-of-monoclonal-gammopathy-of-undetermined-significance-underestimated
#16
Normann Steiner, Angelika Schwärzler, Georg Göbel, Wolfgang Löscher, Julia Wanschitz, Eberhard Gunsilius
OBJECTIVES: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignancy preceding multiple myeloma (MM) or related disorders. Neurological symptoms caused by the monoclonal immunoglobulins or free light-chains are often associated with a high morbidity. We analyzed the prevalence of neuropathy, clinical features and the long-term outcome in 223 patients (pts.) with MGUS. PATIENTS AND METHODS: Between 1/2005 and 3/2015, 223 adult pts. with MGUS were identified in our database...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936757/polyclonal-immunoglobulin-g-n-glycosylation-in-the-pathogenesis-of-plasma-cell-disorders
#17
Stefan Mittermayr, Giao N Lê, Colin Clarke, Silvia Millán Martín, Anne-Marie Larkin, Peter O'Gorman, Jonathan Bones
The pathological progression from benign monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) and finally to active myeloma (MM) is poorly understood. Abnormal immunoglobulin G (IgG) glycosylation in myeloma has been reported. Using a glycomic platform composed of hydrophilic interaction UPLC, exoglycosidase digestions, weak anion-exchange chromatography, and mass spectrometry, polyclonal IgG N-glycosylation profiles from 35 patients [MGUS (n = 8), SMM (n = 5), MM (n = 8), complete-response (CR) post-treatment (n = 5), relapse (n = 4), healthy age-matched control (n = 5)] were characterized to map glycan structures in distinct disease phases of multiple myeloma...
December 12, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27924175/serum-free-light-chain-assay-and-%C3%AE%C2%BA-%C3%AE-ratio-performance-in-patients-with-monoclonal-gammopathy-high-false-negative-rate-for-%C3%AE%C2%BA-%C3%AE-ratio
#18
Gurmukh Singh
BACKGROUND: Serum free light chain assay (SFLCA) and κ/λ ratio, and protein electrophoretic methods are used in the diagnosis and monitoring of monoclonal gammopathies. METHODS: Results for serum free light chains, serum and urine protein electrophoreses and immunofixation electrophoreses in 468 patients with a diagnosis of monoclonal gammopathy were compared. The results of the two methods were graded as concordant, non-concordant or discordant with the established diagnoses to assess the relative performance of the methods...
January 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/27868410/-expression-of-microrna-221-222-in-patients-with-monoclonal-gammopathy-of-undetermined-significance-and-multiple-myeloma
#19
Suwen Yang, Wei Wang, Hong Jin, Yuhong Zhong, Xinyou Xie
Objective: To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27829380/design-and-development-of-the-australian-and-new-zealand-anz-myeloma-and-related-diseases-registry
#20
Krystal Bergin, Elizabeth Moore, Zoe McQuilten, Erica Wood, Bradley Augustson, Hilary Blacklock, Joy Ho, Noemi Horvath, Tracy King, John McNeil, Peter Mollee, Hang Quach, Christopher M Reid, Brian Rosengarten, Patricia Walker, Andrew Spencer
BACKGROUND: Plasma cell dyscrasias (PCD) are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ) for comparison to both local and international guidelines for standards of care...
November 9, 2016: BMC Medical Research Methodology
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