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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/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
#3
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/28070468/multiple-myeloma-associated-chronic-inflammatory-demyelinating-polyradiculoneuropathy-the-importance-of-continued-surveillance
#4
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
#5
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/28061985/multiple-myeloma-epidemiology-and-survival-a-unique-malignancy
#6
REVIEW
Dickran Kazandjian
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation followed by availability of novel treatments such as immunomodulatory drugs (ImIDs) and proteasome inhibitors (PIs) has transformed the natural history of the disease leading to longer survival times...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28040690/obesity-and-the-transformation-of-monoclonal-gammopathy-of-undetermined-significance-to-multiple-myeloma-a-population-based-cohort-study
#7
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/27983725/a-gene-expression-inflammatory-signature-specifically-predicts-multiple-myeloma-evolution-and-patients-survival
#8
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/27974705/are-neurological-complications-of-monoclonal-gammopathy-of-undetermined-significance-underestimated
#9
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
#10
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/27931131/baseline-and-treatment-related-changes-in-thrombin-generation-in-patients-with-multiple-myeloma
#11
Ing S Tiong, Susan E Rodgers, Cindy H S Lee, Simon J McRae
The prothrombotic risk in multiple myeloma (MM) could be potentially assessed by thrombin generation (TG) assays. TG was performed using Calibrated Automated Thrombography with 5 and 1 pM tissue factor. We compared baseline TG among 24 MM patients, 19 MGUS, and 50 healthy controls, and assessed change in TG in MM patients during the initial treatment period at 1, 2, and 3 months. MM subjects demonstrated increased FVIII and VWF:Ag levels pretreatment, and a prothrombotic TG phenotype with increased velocity index, reduced lag time and time-to-peak, and increased resistance to thrombomodulin inhibition...
December 8, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27868410/-expression-of-microrna-221-222-in-patients-with-monoclonal-gammopathy-of-undetermined-significance-and-multiple-myeloma
#12
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
#13
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
https://www.readbyqxmd.com/read/27807648/history-of-autoimmune-disease-is-associated-with-impaired-survival-in-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance-a-population-based-study
#14
Ebba K Lindqvist, Ola Landgren, Sigrún H Lund, Ingemar Turesson, Malin Hultcrantz, Lynn Goldin, Magnus Björkholm, Sigurdur Y Kristinsson
Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls...
February 2017: Annals of Hematology
https://www.readbyqxmd.com/read/27804161/monoclonal-gammopathy-of-undetermined-significance-mgus-and-smoldering-myeloma-smm-a-practical-guide-to-management
#15
Nicola Maciocia, Ashutosh Wechalekar, Kwee Yong
Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are precursor conditions of symptomatic multiple myeloma (MM). Diagnostic principles are aimed at excluding MM requiring therapy, other conditions associated with paraproteins that may require different management, and risk stratifying patients for the purposes of tailored follow-up and investigation. The International Myeloma Working Group have recently published a revised definition of MM, which singles out a small group of patients with smoldering multiple myeloma who are at very high risk of progression and organ damage; such patients are now included under the definition of MM and recommended to start anti-myeloma treatment...
November 2, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27737890/mgus-to-myeloma-a-mysterious-gammopathy-of-underexplored-significance
#16
REVIEW
Madhav V Dhodapkar
All cases of multiple myeloma (MM) are preceded by precursor states termed monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion, wherein tumor cells carry many of the genetic changes found in MM cells. Intraclonal heterogeneity is also established early during the MGUS phase. Although the genetic features of MGUS or SMM cells at baseline may predict disease risk, transition to MM involves altered growth of preexisting clones...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27716740/high-levels-of-periostin-correlate-with-increased-fracture-rate-diffuse-mri-pattern-abnormal-bone-remodeling-and-advanced-disease-stage-in-patients-with-newly-diagnosed-symptomatic-multiple-myeloma
#17
E Terpos, D Christoulas, E Kastritis, T Bagratuni, M Gavriatopoulou, M Roussou, A Papatheodorou, E Eleutherakis-Papaiakovou, N Kanellias, C Liakou, I Panagiotidis, M Migkou, P Kokkoris, L A Moulopoulos, M A Dimopoulos
Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls...
October 7, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27701912/impact-of-metformin-on-the-progression-of-mgus-to-multiple-myeloma
#18
Ben Boursi, Ronac Mamtani, Yu-Xiao Yang, Brendan M Weiss
No abstract text is available yet for this article.
May 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27698801/combined-use-of-free-light-chain-and-heavy-light-chain-ratios-allow-diagnosis-and-monitoring-of-patients-with-monoclonal-gammopathies-experience-of-a-single-institute-with-three-exemplar-case-reports
#19
Alfredo Gagliardi, Claudio Carbone, Angela Russo, Rosanna Cuccurullo, Anna Lucania, Paola Della Cioppa, Gabriella Misso, Michele Caraglia, Catello Tommasino, Lucia Mastrullo
Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite(®) is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite(®) heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27696258/role-of-endothelial-cells-and-fibroblasts-in-multiple-myeloma-angiogenic-switch
#20
Domenico Ribatti, Angelo Vacca
Multiple myeloma (MM) mainly progresses in bone marrow (BM). Therefore, signals from the BM microenvironment are thought to play a critical role in maintaining plasma cell growth, migration, and survival. Reciprocal positive and negative interactions between plasma cells and microenvironmental cells, including endothelial cells (ECs) and fibroblasts may occur. The BM neovascularization is a constant hallmark of MM, and goes hand in hand with progression to leukemic phase. Microenvironmental factors induce MMECs and fibroblasts to become functionally different from monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs), i...
2016: Cancer Treatment and Research
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