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Molecular myeloma

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https://www.readbyqxmd.com/read/28208828/ginkgolic-acid-c-17-1-derived-from-ginkgo-biloba-leaves-suppresses-constitutive-and-inducible-stat3-activation-through-induction-of-pten-and-shp-1-tyrosine-phosphatase
#1
Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seung-Hee Ryu, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28208215/nanoparticle-delivery-systems-general-approaches-and-their-implementation-in-multiple-myeloma
#2
REVIEW
Pilar de la Puente, Abdel Kareem Azab
Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates greater than 90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects. Traditional chemotherapy has shown several disadvantages such as lack of targeting capabilities, systemic toxicity and side effects; low therapeutic index, as well as, most anticancer drugs have poor water solubility...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28205024/immunomodulatory-drugs-in-multiple-myeloma-mechanisms-of-action-and-clinical-experience
#3
REVIEW
Sarah A Holstein, Philip L McCarthy
Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting...
February 16, 2017: Drugs
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#4
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28201976/immunomodulatory-drugs-imids-in-multiple-myeloma
#5
Shahzad Raza, Rachael A Safyan, Lentzsch Suzanne
Multiple myeloma (MM) is a plasma cell neoplasm that is incurable with conventional therapy. However, the treatment of MM has dramatically changed since the emergence of immunomodulatory drugs and proteasome inhibitors. The improvements in survival are linked to a deeper understanding of the molecular mechanisms of the disease. Thalidomide, although highly active in MM, is associated with considerable toxicity, particularly in older patients. Immunomodulatory drugs (IMiDs) are structural and functional analogues of thalidomide that represent a promising new class of immunomodulators for treatment of a variety of inflammatory, autoimmune, and neoplastic diseases...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28198064/real-life-practices-for-preventing-venous-thromboembolism-in-multiple-myeloma-patients-a-cohort-study-from-the-french-health-insurance-database
#6
Aurore Palmaro, Marie-Eve Rougé-Bugat, Martin Gauthier, Fabien Despas, Guillaume Moulis, Maryse Lapeyre-Mestre
PURPOSE: The risk of venous thromboembolic event (VTE) in multiple myeloma is particularly increased. Current guidelines recommend systematic VTE prophylaxis with vitamin K antagonists (VKA) or low weight molecular heparin (LWMH) or unfractionated heparin (UFH) in high-risk patients, based on treatment received [e.g. use of IMiDs (thalidomide, lenalidomide and pomalidomide), alkylating agents or erythropoietin] and individual risk factors (e.g. history of VTE). The aim of this study was to describe strategy of VTE prophylaxis and prescribing of other antithrombotic agents during the first 6 months of multiple myeloma therapy, with stratification on IMiD-based regimens and drug and disease-related risk factors...
February 15, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28164410/hypoxia-inducible-microrna-210-regulates-the-dimt1-irf4-oncogenic-axis-in-multiple-myeloma
#7
Sho Ikeda, Akihiro Kitadate, Fumito Abe, Saitoh Hirobumi, Yoshihiro Michishita, Yoshiaki Hatano, Yoshinari Kawabata, Atsushi Kitabayashi, Kazuaki Teshima, Masaaki Kume, Naoto Takahashi, Hiroyuki Tagawa
Multiple myeloma (MM) is characterized by the accumulation of a population of malignant plasma cells within the bone marrow and its microenvironment. A hypoxic niche is located within the microenvironment, which causes myeloma cells to become quiescent, anti-apoptotic, glycolytic, and immature. Cell heterogeneity may be related to distinct gene expression profiles under hypoxic and normoxic conditions. During hypoxia, myeloma cells acquire these phenotypes by downregulating interferon regulatory factor 4 (IRF4), an essential transcription factor in myeloma oncogenesis...
February 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28151711/gene-expression-profiles-in-myeloma-ready-for-the-real-world
#8
EDITORIAL
Raphael Szalat, Herve Avet-Loiseau, Nikhil C Munshi
Multiple myeloma is a plasma cell malignancy characterized by molecular and clinical heterogeneity. The outcome of the disease has been dramatically improved with the advent of new drugs in the past few years. However, even in this context of increasing therapeutic options, important challenges remain, such as accurately evaluating patients' prognosis and predicting sensitivity to specific treatments and drug combinations. Transcriptomic studies have largely contributed to help decipher multiple myeloma complexity, characterizing multiple myeloma subgroups distinguished by different outcomes...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28151579/mediator-cyclin-dependent-kinases-upregulate-transcription-of-inflammatory-genes-in-cooperation-with-nf-%C3%AE%C2%BAb-and-c-ebp%C3%AE-on-stimulation-of-toll-like-receptor-9
#9
Seiji Yamamoto, Tomoko Hagihara, Yoshiyuki Horiuchi, Akira Okui, Shotaro Wani, Tokuyuki Yoshida, Takao Inoue, Aki Tanaka, Takashi Ito, Yutaka Hirose, Yoshiaki Ohkuma
In eukaryotes, the Mediator complex has important roles in regulation of transcription by RNA polymerase II. Mediator is a large complex with more than 20 subunits that form head, middle, tail and CDK/cyclin modules. Among them, CDK8 and/or CDK19 (CDK8/19), and their counterpart cyclin C, form the CDK/cyclin module together with Mediator subunits MED12 and MED13. Despite evidences of both activation and repression, the precise functional roles of CDK8/19 in transcription are still elusive. Our previous results indicate that CDK8/19 recruits epigenetic regulators to repress immunoresponse genes...
February 2, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28115161/cg13250-a-novel-bromodomain-inhibitor-suppresses-proliferation-of-multiple-myeloma-cells-in-an-orthotopic-mouse-model
#10
Natsuki Imayoshi, Makoto Yoshioka, Jay Chauhan, Susumu Nakata, Yuki Toda, Steven Fletcher, Jeffrey W Strovel, Kazuyuki Takata, Eishi Ashihara
Multiple myeloma (MM) is characterized by the clonal proliferation of neoplastic plasma cells. Despite a stream of new molecular targets based on better understanding of the disease, MM remains incurable. Epigenomic abnormalities contribute to the pathogenesis of MM. bromodomain 4 (BRD4), a member of the bromodomain and extraterminal (BET) family, binds to acetylated histones during M/G1 transition in the cell cycle promoting progression to S phase. In this study, we investigated the effects of a novel BET inhibitor CG13250 on MM cells...
January 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28110970/-plasma-exchange-in-nephrology-indications-and-technique
#11
Christophe Ridel, Sébastien Kissling, Laurent Mesnard, Alexandre Hertig, Éric Rondeau
Plasma exchange is a non-selective apheresis technique that can be performed by filtration or centrifugation allowing rapid purification of high molecular weight pathogens. An immunosuppressive treatment is generally associated to reduce the rebound effect of the purified substance. Substitution solutes such as human albumin and macromolecules are needed to compensate for plasma extraction. Compensation by viro-attenuated plasma is reserved solely for the treatment of thrombotic microangiopathies or when there is a risk of bleeding, because this product is very allergenic and expensive...
January 16, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28104919/next-generation-flow-ngf-for-highly-sensitive-and-standardized-detection-of-minimal-residual-disease-in-multiple-myeloma
#12
J Flores-Montero, L S Flores, B Paiva, N Puig, Omar García-Sánchez, S Böttcher, V H J van der Velden, J-J Pérez-Morán, M-B Vidriales, R García-Sanz, C Jimenez, M González, J Martinez-López, A C Mateos, G-E Grigore, R Fluxá, R Pontes, J Caetano, L Sedek, M-C Del Cañizo, J Bladé, J-J Lahuerta, C Aguilar, A Bárez, A García-Mateo, J Labrador, P Leoz, C Aguilera-Sanz, J San-Miguel, M-V Mateos, B Durie, J J M van Dongen, A Orfao
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly-sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign...
January 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28100400/replication-study-bet-bromodomain-inhibition-as-a-therapeutic-strategy-to-target-c-myc
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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