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Molecular myeloma

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https://www.readbyqxmd.com/read/28100400/replication-study-bet-bromodomain-inhibition-as-a-therapeutic-strategy-to-target-c-myc
#1
Fraser Aird, Irawati Kandela, Christine Mantis
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper "BET bromodomain inhibition as a therapeutic strategy to target c-Myc" (Delmore et al., 2011). Here we report the results of those experiments. We found that treatment of human multiple myeloma (MM) cells with the small-molecular inhibitor of BET bromodomains, (+)-JQ1, selectively downregulated MYC transcription, which is similar to what was reported in the original study (Figure 3B; Delmore et al...
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28078910/gain-of-chromosome-1q-portends-worse-prognosis-in-multiple-myeloma-despite-novel-agent-based-induction-regimens-and-autologous-transplantation
#2
Gunjan L Shah, Heather Landau, Dory Londono, Sean M Devlin, Satyajit Kosuri, Alexander M Lesokhin, Nikoletta Lendvai, Hani Hassoun, David J Chung, Guenther Koehne, Suresh C Jhanwar, Ola Landgren, Ross Levine, Sergio A Giralt
We aimed to identify whether the use of autologous hematopoietic cell transplantation (HCT) impacts outcomes for multiple myeloma patients with gains of chromosome 1q (+1q). We retrospectively identified 95 patients, 21% having +1q. For patients with +1q, the overall response rate to induction was 85%, with 40% having ≥ VGPR and 20% achieving a CR, similar to non +1q patients (p = .64). The median PFS from diagnosis with +1q was 2.1 years (95% CI: 1.2-not reached (NR)) vs 4.3 years (95% CI: 3...
January 12, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28061986/a-look-backward-and-forward-in-the-regulatory-and-treatment-history-of-multiple-myeloma-approval-of-novel-novel-agents-new-drug-development-and-longer-patient-survival
#3
REVIEW
Dickran Kazandjian, Ola Landgren
The past decade has seen significant advances in our understanding and treatment of multiple myeloma (MM) and its precursor diseases. These advances include gains in knowledge of the underlying pathobiology including molecular and cellular prognostic factors for disease progression. In parallel we have witnessed the availability of novel therapeutics. Together these advances have translated into improvements in long-term clinical benefit and survival in MM. Indeed, it has been shown that patients diagnosed in the last decade have experienced almost doubling of median survival time...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28052121/molecular-characteristics-of-high-dose-melphalan-associated-oral-mucositis-in-patients-with-multiple-myeloma-a-gene-expression-study-on-human-mucosa
#4
Mette Marcussen, Julie Støve Bødker, Heidi Søgaard Christensen, Preben Johansen, Søren Nielsen, Ilse Christiansen, Olav Jonas Bergmann, Martin Bøgsted, Karen Dybkær, Mogens Vyberg, Hans Erik Johnsen
BACKGROUND: Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis. METHODS AND FINDINGS: Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration...
2017: PloS One
https://www.readbyqxmd.com/read/28028022/multiple-myeloma-cells-capacity-to-decompose-h2o2-determines-lenalidomide-sensitivity
#5
Sinto Sebastian, Yuan X Zhu, Esteban Braggio, Chang-Xin Shi, Sonali C Panchabhai, Scott A Van Wier, Greg J Ahmann, Marta Chesi, P Leif Bergsagel, A Keith Stewart, Rafael Fonseca
Lenalidomide is an immunomodulatory drug (IMiDs) with clinical efficacy in multiple myeloma (MM) and other late B-cell neoplasms. Although cereblon (CRBN) is an essential requirement for IMiD action, the complete molecular and biochemical mechanisms responsible for lenalidomide-mediated sensitivity or resistance remain unknown. Here, we report that IMiDs work primarily via inhibition of peroxidase-mediated intracellular H2O2 decomposition in MM cells. MM cells with lower H2O2-decomposition capacity were more vulnerable to lenalidomide-induced H2O2 accumulation and associated cytotoxicity...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28024628/polypropyleneimine-and-polyamidoamine-dendrimer-mediated-enhanced-solubilization-of-bortezomib-comparison-and-evaluation-of-mechanistic-aspects-by-thermodynamics-and-molecular-simulations
#6
Sonam Chaudhary, Avinash Gothwal, Iliyas Khan, Shubham Srivastava, Ruchi Malik, Umesh Gupta
Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i...
March 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28024514/-advances-of-crbn-in-immunomodulatory-drugs-for-multiple-myeloma-review
#7
Ran An, Jian Hou
Multiple myeloma is a plasma cell malignant clone proliferation diseases and has been remained incurable. In the resent years, the widespread application of immunomodulatory drugs (IMiD) have made a great progress in the treatment of multiple myeloma, greatly improved the complete remission rate and prolonged the overall survival of MM patients. According to recent researches, CRBN (cereblon) plays an important role in mediating anti-myeloma effects of IMiD, and its expression correlated with the effect of IMiD treatment and the prognosis of multiple myeloma...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28008668/immunoglobulin-heavy-and-light-chains-and-t-cell-receptor-beta-and-gamma-chains-pcr-assessment-on-cytological-samples-a-study-comparing-fta-cards-and-cryopreserved-lymph-node-fine-needle-cytology
#8
A L Peluso, I Cozzolino, A Bottiglieri, L Lucchese, R M Di Crescenzo, M Langella, C Selleri, P Zeppa
OBJECTIVES: To evaluate and compare the DNA yield and quality extracted from lymph node fine needle cytology (FNC) samples stored on FTA cards to those cryopreserved, and to assess the immunoglobulin heavy and light chains (IGHK) and T-Cell receptor beta and gamma chains (TCRBG) PCR tests. METHODS: DNA extractions were performed on FNC of 80 non-Hodgkin lymphomas (NHL), four myelomas and 56 benign reactive hyperplasias (BRH) cryopreserved and stored on FTA cards...
December 22, 2016: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/27930986/plant-derived-flavone-apigenin-the-small-molecule-with-promising-activity-against-therapeutically-resistant-prostate-cancer
#9
REVIEW
Shabir Ahmad Ganai
Prostate cancer is the second leading cause of cancer related deaths in men in the United States. Mounting evidences suggest that in the pathophysiology of prostate cancer epigenetic modifications play a considerable role. Histone deacetylases (HDACs) have strong crosstalk with prostate cancer progression as they regulate various genes meant for tumour suppression. HDACs are emerging as striking molecular targets for anticancer drugs and therapy as their aberrant expression has been implicated in several cancers...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27926524/selective-hdac-inhibition-by-acy-241-enhances-the-activity-of-paclitaxel-in-solid-tumor-models
#10
Pengyu Huang, Ingrid Almeciga-Pinto, Matthew Jarpe, John H van Duzer, Ralph Mazitschek, Min Yang, Simon S Jones, Steven N Quayle
ACY-241 is a novel, orally available and selective histone deacetylase (HDAC) 6 inhibitor in Phase 1b clinical development in multiple myeloma (NCT 02400242). Like the structurally related drug ACY-1215 (ricolinostat), ACY-241 has the potential for a substantially reduced side effect profile versus current nonselective HDAC inhibitor drug candidates due to reduced potency against Class I HDACs while retaining the potential for anticancer effectiveness. We now show that combination treatment of xenograft models with paclitaxel and either ricolinostat or ACY-241 significantly suppresses solid tumor growth...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#11
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
#12
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
#13
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
#14
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
#15
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...
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
#16
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
#17
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...
January 2017: 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
#18
Cristina Jiménez, María Jara-Acevedo, Luis A Corchete, David Castillo, Gonzalo R Ordóñez, María E Sarasquete, Noemí Puig, Joaquín Martínez-López, María I Prieto-Conde, María García-Álvarez, María C 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...
January 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27856369/outcomes-of-maintenance-therapy-with-bortezomib-after-autologous-stem-cell-transplantation-for-patients-with-multiple-myeloma
#19
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 after 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 with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015...
February 2017: 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
#20
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...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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