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Molecular myeloma

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https://www.readbyqxmd.com/read/28429672/the-molecular-mechanisms-of-thalidomide-teratogenicity-and-implications-for-modern-medicine
#1
J Knobloch, D Jungck, A Koch
Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and anti-angiogenic activities are considered in many other refractory diseases...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28428191/the-role-of-minimal-residual-disease-testing-in-myeloma-treatment-selection-and-drug-development-current-value-and-future-applications
#2
Kenneth C Anderson, Daniel Auclair, Gary J Kelloff, Caroline C Sigman, Herve Avet-Loiseau, Ann T Farrell, Nicole J Gormley, Shaji K Kumar, Ola Landgren, Nikhil C Munshi, Michele Cavo, Faith E Davies, Alessandra Di Bacco, Jennifer S Dickey, Steven I Gutman, Howard R Higley, Mohamad A Hussein, J Milburn Jessup, Ilan R Kirsch, Richard F Little, Robert D Loberg, Jens G Lohr, Lata Mukundan, James L Omel, Trevor J Pugh, Gregory H Reaman, Michael D Robbins, A Kate Sasser, Nancy Valente, Elena Zamagni
Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10(-5)‒10(-6) cells...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28427158/the-varied-distribution-and-impact-of-ras-codon-and-other-key-dna-alterations-across-the-translocation-cyclin-d-subgroups-in-multiple-myeloma
#3
Caleb K Stein, Charlotte Pawlyn, Shweta Chavan, Leo Rasche, Niels Weinhold, Adam Corken, Amy Buros, Pieter Sonneveld, Graham H Jackson, Ola Landgren, Tariq Mughal, Jie He, Bart Barlogie, P Leif Bergsagel, Faith E Davies, Brian A Walker, Gareth J Morgan
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425752/use-of-standard-laboratory-methods-to-obviate-routine-dithiothreitol-treatment-of-blood-samples-with-daratumumab-interference
#4
Nicholas J Lintel, Debra K Brown, Diane T Schafer, Farai M Tsimba-Chitsva, Scott A Koepsell, Sara M Shunkwiler
Daratumumab is an antibody currently used in the treatment of patients with refractory multiple myeloma. Blood samples from patients being treated with daratumumab may show panreactivity during pre-transfusion testing. To facilitate the provision of blood components for such patients, it is recommended that a baseline phenotype or genotype be established prior to starting treatment with daratumumab. If patient red blood cells (RBCs) require phenotyping after the start of daratumumab treatment, dithiothreitol (DTT) treatment of the patient's RBCs should be performed...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28405503/genotoxic-stress-modulates-the-release-of-exosomes-from-multiple-myeloma-cells-capable-of-activating-nk-cell-cytokine-production-role-of-hsp70-tlr2-nf-kb-axis
#5
Elisabetta Vulpis, Francesca Cecere, Rosa Molfetta, Alessandra Soriani, Cinzia Fionda, Giovanna Peruzzi, Giulio Caracciolo, Sara Palchetti, Laura Masuelli, Lucilla Simonelli, Ugo D'Oro, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rossella Paolini, Marco Cippitelli, Angela Santoni, Alessandra Zingoni
Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404951/search-for-rare-protein-altering-variants-influencing-susceptibility-to-multiple-myeloma
#6
Matthew Scales, Daniel Chubb, Sara E Dobbins, David C Johnson, Ni Li, Michael J Sternberg, Neils Weinhold, Caleb Stein, Graham Jackson, Faith E Davies, Brian A Walker, Christopher P Wardell, Richard S Houlston, Gareth J Morgan
The genetic basis underlying the inherited risk of developing multiple myeloma (MM) is largely unknown. To examine the impact of rare protein altering variants on the risk of developing MM we analyzed high-coverage exome sequencing data on 513 MM cases and 1,569 healthy controls, performing both single variant and gene burden tests. We did not identify any recurrent coding low-frequency alleles (1-5%) with moderate effect that were statistically associated with MM. In a gene burden analysis we did however identify a promising relationship between variation in the marrow kinetochore microtubule stromal gene KIF18A, which plays a role in control mitotic chromosome positioning dynamics, and risk of MM (P =3...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399389/anthelmintic-flubendazole-and-its-potential-use-in-anticancer-therapy
#7
Kristýna Čáňová, Lucie Rozkydalová, Emil Rudolf
Flubendazole is a widely used anthelmintic drug belonging to benzimidazole group. The molecular mechanism of action of flubendazole is based on its specific binding to tubulin, which results in disruption of microtubule structure and function, and in the interference with the microtubule-mediated transport of secretory vesicles in absorptive tissues of helminths. The microtubule-disrupting properties of benzimidazole derivatives raised recently interest in these compounds as possible anti-cancer agents. In this minireview flubendazole effects towards selected human malignant cells including myeloma, leukemia, neuroblastoma, breast cancer, colorectal cancer and melanoma are discussed along with basic data on its pharmacokinetics, metabolism and toxicity...
April 11, 2017: Acta Medica (Hradec Králové)
https://www.readbyqxmd.com/read/28392342/exploitation-of-human-cd99-expressing-mouse-myeloma-cells-as-immunogen-for-production-of-mouse-specific-polyclonal-antibodies
#8
Nuchjira Takheaw, Witida Laopajon, Kantinan Chuensirikulchai, Watchara Kasinrerk, Supansa Pata
In this study, we describe the application of a molecular biology technique for the production of mouse polyclonal antibodies (pAbs) specific to human cell surface molecules. Production of the pAb specific to the human CD99 surface molecule was used as the study model. The retroviral expression system was employed to generate human CD99 expressing mouse myeloma cells. After cell sorting and single cell cloning, a myeloma clone which stably expressed high levels of human CD99 on its surface was established. The human CD99 expressing mouse myeloma cells were then used as the immunogen for immunization of BALB/c mice...
April 6, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28378636/potential-prognostic-long-non-coding-rna-identification-and-their-validation-in-predicting-survival-of-patients-with-multiple-myeloma
#9
Ai-Xin Hu, Zhi-Yong Huang, Lin Zhang, Jian Shen
Multiple myeloma, a typical hematological malignancy, is characterized by malignant proliferation of plasma cells. This study was to identify differently expressed long non-coding RNAs to predict the survival of patients with multiple myeloma efficiently. Gene expressing profiles of diagnosed patients with multiple myeloma, GSE24080 (559 samples) and GSE57317 (55 samples), were downloaded from Gene Expression Omnibus database. After processing, survival-related long non-coding RNAs were identified by Cox regression analysis...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28373875/roles-and-modalities-of-ectonucleotidases-in-remodeling-the-multiple-myeloma-niche
#10
Antonella Chillemi, Valeria Quarona, Luca Antonioli, Davide Ferrari, Alberto L Horenstein, Fabio Malavasi
Ectoenzymes are cell surface molecules, which represent functional bridges between the environment and the cytoplasm. One set of ectoenzymes-CD39, CD38, CD203a, and CD73-leads to the generation of adenosine (ADO) by metabolizing ATP and NAD(+). While ADO is known to control inflammation and suppress immune responses, other aspects of ADO function are still obscure, mainly due to its short half-life in biological fluids. Human multiple myeloma (MM) grows in the closed system of the bone marrow (BM) niche representing an ideal setting for studying ectoenzymes and their products...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28362441/overexpression-of-ezh2-in-multiple-myeloma-is-associated-with-poor-prognosis-and-dysregulation-of-cell-cycle-control
#11
C Pawlyn, M D Bright, A F Buros, C K Stein, Z Walters, L I Aronson, F Mirabella, J R Jones, M F Kaiser, B A Walker, G H Jackson, P A Clarke, P L Bergsagel, P Workman, M Chesi, G J Morgan, F E Davies
Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly defined high-risk patients who continue to do badly. Novel therapeutic approaches are, therefore, required. A growing number of epigenetic inhibitors are now available including EZH2 inhibitors that are in early-stage clinical trials for treatment of haematological and other cancers with EZH2 mutations or in which overexpression has been correlated with poor outcomes...
March 31, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28359248/immunomodulatory-activity-of-micrornas-potential-implications-for-multiple-myeloma-treatment
#12
Cirino Botta, Maria Cucè, Daniele Caracciolo, Lucia Fiorillo, Pierosandro Tagliaferri, Pierfrancesco Tassone
Multiple myeloma (MM) is an incurable plasma cell neoplasm accounting for about 10% of all hematologic malignancies. Recently, emerging evidence is disclosing the complexity of bone marrow interactions between MM cells and infiltrating immune cells, which have been reported to promote proliferation, survival and drug resistance of tumor cells. MicroRNAs (miRNAs) are small non-coding RNA molecules with regulatory functions in the cell, whose expression has predictive and prognostic value in different malignancies...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28351297/epha4-promotes-cell-proliferation-and-cell-adhesion-mediated-drug-resistance-via-the-akt-pathway-in-multiple-myeloma
#13
Linlin Ding, Yaodong Shen, Jing Ni, Yiqing Ou, Yangyu Ou, Hong Liu
Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular (Eph) family, has been reported to upregulate in several tumors. However, the role of EphA4 in multiple myeloma has not been clarified yet. In this study, we found that EphA4 promoted proliferation of multiple myeloma cells via the regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of multiple myeloma cells and promoted cell adhesion-mediated drug resistance by enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple myeloma...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28316846/donor-derived-smoldering-multiple-myeloma-following-a-hematopoietic-cell-transplantation-for-aml
#14
Bita Fakhri, Mark Fiala, Michael Slade, Peter Westervelt, Armin Ghobadi
Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28316065/identification-of-key-genes-and-construction-of-microrna-mrna-regulatory-networks-in-multiple-myeloma-by-integrated-multiple-geo-datasets-using-bioinformatics-analysis
#15
Hongyu Gao, Huihan Wang, Wei Yang
Multiple myeloma (MM) is a common hematological malignancy. To identify key genes and microRNAs in MM, we downloaded two gene expression profiles (GSE16558 and GSE47552) and two microRNA expression profiles (GSE17498 and GSE16558) from the Gene Expression Omnibus (GEO) database. A total of 596 differentially expressed genes (DEGs) and 39 differentially expressed microRNAs (DEMs) were screened out. Pathway analysis showed that upregulated genes were mainly enriched in the "B cell receptor signaling pathway", "Cell cycle" and "NF-kappa B signaling pathway", whereas downregulated genes were mainly enriched in the "Ribosome", "FoxO signaling pathway" and "p53 signaling pathway"...
March 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28304351/the-preparation-and-identification-of-a-monoclonal-antibody-against-citrinin-and-the-development-of-detection-via-indirect-competitive-elisa
#16
Shimuye Kalayu Yirga, Sumei Ling, Yanling Yang, Jun Yuan, Shihua Wang
Citrinin (CTN) is a hepato-nephrotoxic mycotoxin produced by fungi genera of Aspergillus, Monauscus, and Penicillium. CTN contaminates grains, fruits, juices and vegetables, and causes various toxic effects to humans and animals. It has small molecular weight, which is non-immunogenic to animals. Thus, CTN was conjugated to bovine serum albumin (BSA) and ovalbumin (OVA), respectively, by amide bonds using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Mice were immunized with CTN-BSA conjugates, and spleen cells of the immunized mice were fused with Sp2/0 myeloma cells to obtain 21H27 hybriodoma cell...
March 17, 2017: Toxins
https://www.readbyqxmd.com/read/28301380/nitroxoline-shows-antimyeloma-activity-by-targeting-the-trim25-p53-axle
#17
Hongwu Mao, Yanyun Du, Zubin Zhang, Biyin Cao, Jun Zhao, Haibin Zhou, Xinliang Mao
The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28285807/a-brighter-side-to-thalidomide-its-potential-use-in-immunological-disorders
#18
REVIEW
David Millrine, Tadamitsu Kishimoto
Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD)...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28282510/cxcr4-cd184-expression-on-stem-cell-harvest-and-cd34-cells-post-transplant
#19
Inas Asfour, Hanaa Afify, Shaza Elkourashy, Maryse Ayoub, Gihan Kamal, Mary Gamal, Ghada Elgohary
OBJECTIVES/BACKGROUND: CXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism. METHODS: This is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014...
March 2, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28280367/clarifying-the-molecular-mechanism-associated-with-carfilzomib-resistance-in-human-multiple-myeloma-using-microarray-gene-expression-profile-and-genetic-interaction-network
#20
Zhihong Zheng, Tingbo Liu, Jing Zheng, Jianda Hu
Carfilzomib is a Food and Drug Administration-approved selective proteasome inhibitor for patients with multiple myeloma (MM). However, recent studies indicate that MM cells still develop resistance to carfilzomib, and the molecular mechanisms associated with carfilzomib resistance have not been studied in detail. In this study, to better understand its potential resistant effect and its underlying mechanisms in MM, microarray gene expression profile associated with carfilzomib-resistant KMS-11 and its parental cell line was downloaded from Gene Expression Omnibus database...
2017: OncoTargets and Therapy
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