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Molecular myeloma

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https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#1
REVIEW
Ana B Herrero, Elizabeta A Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski, Norma C Gutiérrez
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#2
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#3
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27910767/immunostimulatory-effects-of-melphalan-and-usefulness-in-adoptive-cell-therapy-with-antitumor-cd4-t-cells
#4
Michal Kuczma, Zhi-Chun Ding, Gang Zhou
The alkylating agent melphalan is used in the treatment of hematological malignancies, especially multiple myeloma. In the past, the usefulness of melphalan has been solely attributed to its cytotoxicity on fastgrowing cancerous cells. Although the immunomodulatory effects of melphalan were suggested many years ago, only recently has this aspect of melphalan's activity begun to be elucidated at the molecular level. Emerging evidence indicates that melphalan can foster an immunogenic microenvironment by inducing immunogenic cell death (ICD) as characterized by membrane translocation of endoplasmic reticulum protein calreticulin (CRT) and by release of chromatin-binding protein high-mobility group box 1 (HMGB1)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27906452/primary-prophylaxis-for-venous-thromboembolism-in-ambulatory-cancer-patients-receiving-chemotherapy
#5
REVIEW
Marcello Di Nisio, Ettore Porreca, Matteo Candeloro, Michele De Tursi, Ilaria Russi, Anne Ws Rutjes
BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis...
December 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#6
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27892767/epigenetic-modifications-in-multiple-myeloma-recent-advances-on-the-role-of-dna-and-histone-methylation
#7
Nicola Amodio, Patrizia D'Aquila, Giuseppe Passarino, Pierfrancesco Tassone, Dina Bellizzi
Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway...
November 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27863261/a-next-generation-sequencing-strategy-for-evaluating-the-most-common-genetic-abnormalities-in-multiple-myeloma
#8
Cristina Jiménez, María Jara-Acevedo, Luis A Corchete, David Castillo, Gonzalo R Ordóñez, M Eugenia Sarasquete, Noemí Puig, Joaquín Martínez-López, M Isabel Prieto-Conde, María García-Álvarez, M Carmen Chillón, Ana Balanzategui, Miguel Alcoceba, Albert Oriol, Laura Rosiñol, Luis Palomera, Ana I Teruel, Juan J Lahuerta, Joan Bladé, María V Mateos, Alberto Orfão, Jesús F San Miguel, Marcos González, Norma C Gutiérrez, Ramón García-Sanz
Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions...
November 15, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27856369/outcomes-of-maintenance-therapy-with-bortezomib-post-autologous-stem-cell-transplantation-for-patients-with-multiple-myeloma
#9
Dharshan Sivaraj, Michael M Green, Zhiguo Li, Anthony D Sung, Stefanie Sarantopoulos, Yubin Kang, Gwynn D Long, Mitchell E Horwitz, Richard D Lopez, Keith M Sullivan, David A Rizzieri, Nelson J Chao, Cristina Gasparetto
Comprehensive recommendations for maintenance therapy post-autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared to lenalidomide in the post-ASCT setting are limited. Therefore we retrospectively analyzed the outcomes of 102 MM patients who received maintenance therapy with bortezomib post-ASCT at Duke University's Adult Bone Marrow Transplant Clinic (ABMT) between 2005 and 2015...
November 14, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27842905/mir-148a-participates-in-the-growth-of-rpmi8226-multiple-myeloma-cells-by-regulating-cdkn1b
#10
Tao Lang, Yuling Nie
OBJECTIVE: The aim of this study is to explore the influence of miR-148a on cell proliferation and cell cycle of multiple myeloma (MM) cell line RPMI8226 and the related molecular mechanism. METHODS: The expression of miR-148a and CDKN1B in MM cells and primary cells of normal bone marrow were determined by RT-PCR and western blotting. The cell proliferation and cell cycle of miR-148a knockdown MM cells and normal MM cells were determined by flow cytometry. The protein expression of p-NPAT, p-Rb and p-CDC6 was determined in normal and miR-148a knockdown MM cells...
November 11, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27806731/in-vitro-assessment-of-a-computer-designed-potential-anticancer-agent-in-cervical-cancer-cells
#11
Michelle Helen Visagie, Seema Rummurat Jaiswal, Anna Margaretha Joubert
BACKGROUND: Computer-based technology is becoming increasingly essential in biological research where drug discovery programs start with the identification of suitable drug targets. 2-Methoxyestradiol (2ME2) is a 17β-estradiol metabolite that induces apoptosis in various cancer cell lines including cervical cancer, breast cancer and multiple myeloma. Owing to 2ME2's poor in vivo bioavailability, our laboratory in silico-designed and subsequently synthesized a novel 2ME2 analogue, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol), using receptor- and ligand molecular modeling...
November 2, 2016: Biological Research
https://www.readbyqxmd.com/read/27793878/maf-protein-mediates-innate-resistance-to-proteasome-inhibition-therapy-in-multiple-myeloma
#12
Ya-Wei Qiang, Shiqiao Ye, Yu Chen, Amy F Buros, Ricky Edmonson, Frits Van Rhee, Bart Barlogie, Joshua Epstein, Gareth J Morgan, Faith E Davies
Multiple myeloma (MM) patients with the t(14;16) translocation have a poor prognosis, and unlike other molecular subgroups, their outcome has not improved with the introduction of bortezomib. The mechanism underlying innate resistance of MM to bortezomib is unknown. In the present study, we have investigated how MAF overexpression impacts resistance to proteasome inhibitor (PI) therapy (bortezomib and carfilzomib). High levels of MAF protein were found in t(14;16) cell lines, cell lines from the t(4;14) subgroup had intermediate levels, while cell lines from the other subgroups had low levels...
October 28, 2016: Blood
https://www.readbyqxmd.com/read/27792246/inhibition-of-histone-deacetylases-in-melanoma-a-perspective-from-bench-to-bedside
#13
REVIEW
Eva Hornig, Markus V Heppt, Saskia A Graf, Thomas Ruzicka, Carola Berking
Histone deacetylases (HDACs) are critically involved in epigenetic gene regulation through alterations of the chromatin status of DNA. Aberrant expression, dysregulation of their enzymatic activity or imbalances between HDACs and histone acetyltransferases are likely involved in the development and progression of cancer. Pharmacologic inhibition of HDACs shows potent antitumor activity in a panel of malignancies such as colon or gastric cancer and multiple myeloma. In this review, we summarize the current knowledge of HDACs in melanoma and evaluate the application of HDAC inhibition from an experimental and clinical perspective...
November 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27779105/minimal-residual-disease-after-transplantation-or-lenalidomide-based-consolidation-in-myeloma-patients-a-prospective-analysis
#14
Stefania Oliva, Manuela Gambella, Milena Gilestro, Vittorio Emanuele Muccio, Francesca Gay, Daniela Drandi, Simone Ferrero, Roberto Passera, Chiara Pautasso, Annalisa Bernardini, Mariella Genuardi, Francesca Patriarca, Elona Saraci, Maria Teresa Petrucci, Norbert Pescosta, Anna Marina Liberati, Tommaso Caravita, Concetta Conticello, Alberto Rocci, Pellegrino Musto, Mario Boccadoro, Antonio Palumbo, Paola Omedè
We analyzed 50 patients who achieved at least a very good partial response in the RV-MM-EMN-441 study. Patients received consolidation with autologous stem-cell transplantation (ASCT) or cyclophosphamide-lenalidomide-dexamethasone (CRD), followed by Lenalidomide-based maintenance. We assessed minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) after consolidation, after 3 and 6 courses of maintenance, and thereafter every 6 months until progression...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27754828/small-interfering-rna-mediated-silencing-of-nicotinamide-phosphoribosyltransferase-nampt-and-lysosomal-trafficking-regulator-lyst-induce-growth-inhibition-and-apoptosis-in-human-multiple-myeloma-cells-a-preliminary-study
#15
Ivyna Pau Ni Bong, Ching Ching Ng, Shaik Kamal Fakiruddin, Moon Nian Lim, Zubaidah Zakaria
Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers...
November 10, 2016: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27745940/-macro-ast-and-myeloma-an-incidental-association
#16
C Lartigau-Roussin, M H Paclet, H Audin, B Toussaint, T Henni, L Raffray
INTRODUCTION: Macro-AST is recognized as a classical aetiology of isolated and persistent increase of serum aspartate aminotransferase (AST) levels. Macro-AST are high molecular weight complexes associating AST and a macromolecule, often an immunoglobulin. Although those macroenzymes of unknown pathogenesis are usually non-pathogenic, association with several diseases, including autoimmune diseases and liver diseases has been described. CASE REPORT: We report here the case of a 45-year-old patient with previously normal liver enzymes in whom an AST elevation and an IgA monoclonal gammopathy were discovered concomitantly...
October 13, 2016: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/27742710/caspase-3-dependent-cleavage-of-bcl-xl-in-the-stroma-exosomes-is-required-for-their-uptake-by-hematological-malignant-cells
#17
Ioulia Vardaki, Claire Sanchez, Pedro Fonseca, Magnus Olsson, Dimitrios Chioureas, George Rassidakis, Anders Ullén, Boris Zhivotovsky, Magnus Björkholm, Theocharis Panaretakis
The intercellular crosstalk between hematological malignancies and the tumor microenvironment is mediated by cell to cell interactions and soluble factors. One component of the secretome that is gaining increasing attention are the extracellular vesicles and in particular the exosomes. Apart from the role as vectors of molecular information, exosomes have been shown to possess intrinsic biological activity. In this study we have found that caspase-3 is activated in L88 bone marrow stroma cell-derived exosomes and identified one of the substrates to be the anti-apoptotic protein Bcl-xL...
October 14, 2016: Blood
https://www.readbyqxmd.com/read/27721294/primary-plasma-cell-leukemia-a-report-of-two-cases-of-a-rare-and-aggressive-variant-of-plasma-cell-myeloma-with-the-review-of-literature
#18
Prithal Gangadhar, Zulfikar Ahmed, Muktha R Pai, I Sandhya
Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma accounting for 2-3% of all plasma cell dyscrasias characterized by the presence of circulating plasma cells. The diagnosis is based on the % (≥20%) and absolute number (≥2x10 9 /L) of plasma cells in the peripheral blood. The incidence of primary PCL (pPCL) is very rare and reported to occur in <1 in a million. It is classified as either pPCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. pPCL is a distinct clinicopathological entity with different cytogenetic and molecular findings...
October 2016: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/27713531/translation-elongation-factor-eef1a2-is-a-novel-anticancer-target-for-the-marine-natural-product-plitidepsin
#19
Alejandro Losada, María José Muñoz-Alonso, Carolina García, Pedro A Sánchez-Murcia, Juan Fernando Martínez-Leal, Juan Manuel Domínguez, M Pilar Lillo, Federico Gago, Carlos M Galmarini
eEF1A2 is one of the isoforms of the alpha subunit of the eukaryotic Elongation Factor 1. It is overexpressed in human tumors and is endowed with oncogenic properties, favoring tumor cell proliferation while inhibiting apoptosis. We demonstrate that plitidepsin, an antitumor agent of marine origin that has successfully completed a phase-III clinical trial for multiple myeloma, exerts its antitumor activity by targeting eEF1A2. The drug interacts with eEF1A2 with a KD of 80 nM and a target residence time of circa 9 min...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27707673/cytogenetics-in-the-management-of-multiple-myeloma-an-update-by-the-groupe-francophone-de-cytog%C3%A3-n%C3%A3-tique-h%C3%A3-matologique-gfch
#20
Agnès Daudignon, Benoît Quilichini, Geneviève Ameye, Hélène Poirel, Christian Bastard, Christine Terré
Cytogenetics of multiple myeloma has evolved in recent years by the emergence of Interphasic fluorescence in situ hybridization (FISH) performed on sorted plasma cells detecting abnormalities independently of a proliferative and infiltrative index. Cytogenetic analysis plays a major part in the risk stratification of myeloma diagnosis due to prognostic impact of various cytogenetic abnormalities as well as to the association between emerging therapeutic approaches in MM. Thus, practice guidelines now recommend interphasic FISH or alternative molecular technics as the initial analysis for multiple myeloma...
October 1, 2016: Annales de Biologie Clinique
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