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https://www.readbyqxmd.com/read/29907806/final-outcomes-of-escalated-melphalan-280-mg-m-2-with-amifostine-cytoprotection-followed-autologous-hematopoietic-stem-cell-transplantation-for-multiple-myeloma-high-cr-and-vgpr-rates-do-not-translate-into-improved-survival
#1
Parameswaran Hari, Donna E Reece, Jasleen Randhawa, Neal Flomenberg, Dianna S Howard, Ashrof Z Badros, Aaron P Rapoport, Barry R Meisenberg, Joanne Filicko-Ohara, Gordon L Phillips, David H Vesole
The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220-260 mg/m2 , although relatively well tolerated, have not shown significant improvement in clinical outcomes. Several approaches have been pursued in the past to improve CR rates, including poly-chemotherapy preparative regimens, tandem ASCT, consolidation, and/or maintenance therapy. Since there is a steep dose-response effect for intravenous melphalan, we evaluated an alternative single ASCT strategy using higher-dose melphalan at 280 mg/m2 (MEL 280) with amifostine as a cytoprotectant as the maximum tolerated dose determined in an earlier phase I dose escalation trial...
June 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29907552/beyond-maximum-grade-modernising-the-assessment-and-reporting-of-adverse-events-in-haematological-malignancies
#2
REVIEW
Gita Thanarajasingam, Lori M Minasian, Frederic Baron, Franco Cavalli, R Angelo De Claro, Amylou C Dueck, Tarec C El-Galaly, Neil Everest, Jan Geissler, Christian Gisselbrecht, John Gribben, Mary Horowitz, S Percy Ivy, Caron A Jacobson, Armand Keating, Paul G Kluetz, Aviva Krauss, Yok Lam Kwong, Richard F Little, Francois-Xavier Mahon, Matthew J Matasar, María-Victoria Mateos, Kristen McCullough, Robert S Miller, Mohamad Mohty, Philippe Moreau, Lindsay M Morton, Sumimasa Nagai, Simon Rule, Jeff Sloan, Pieter Sonneveld, Carrie A Thompson, Kyriaki Tzogani, Flora E van Leeuwen, Galina Velikova, Diego Villa, John R Wingard, Sophie Wintrich, John F Seymour, Thomas M Habermann
Tremendous progress in treatment and outcomes has been achieved across the whole range of haematological malignancies in the past two decades. Although cure rates for aggressive malignancies have increased, nowhere has progress been more impactful than in the management of typically incurable forms of haematological cancer. Population-based data have shown that 5-year survival for patients with chronic myelogenous and chronic lymphocytic leukaemia, indolent B-cell lymphomas, and multiple myeloma has improved markedly...
June 12, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29907543/acute-liver-failure-associated-with-pomalidomide-therapy-for-multiple-myeloma
#3
Lauren Reed-Guy, Maarouf A Hoteit, Alfred L Garfall
No abstract text is available yet for this article.
May 26, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29907380/monoclonal-gammopathies-of-unknown-significance-and-smoldering-myeloma-assessment-and-management-of-the-elderly-patients
#4
Verónica González-Calle, María Victoria Mateos
Monoclonal gammopathy of unknown significance (MGUS) is the most frequent plasma cell disorder that commonly affects elderly patients. Although it is an asymptomatic condition, as well as smoldering myeloma (SMM), the risk of progression to multiple myeloma requiring therapy or other B-cell disorders varies greatly for individual patients, remaining low for MGUS (1% per year), while higher and not uniform for SMM patients (10% per year). This scenario implies some special considerations regarding assessment and follow-up, especially in the elderly...
June 12, 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29907292/nanobody-based-dual-epitopes-protein-identification-depid-assay-for-measuring-soluble-cd38-in-plasma-of-multiple-myeloma-patients
#5
Ting Li, Song Lu Li, Cheng Fang, Yun Nan Hou, Qiaoxia Zhang, Xin Du, Hon Cheung Lee, Yong Juan Zhao
BACKGROUND: CD38 is a surface membrane antigen highly expressed in malignant blood cells, such as multiple myeloma (MM). A soluble form of CD38 (sCD38) is also present in the plasma, deriving likely from the shedding from the cells. The plasma levels of sCD38 should thus correlate closely with the proliferation of the MM cells, allowing the development of a simple diagnostic blood test for monitoring the progress of the disease. However, the plasma sCD38 levels are extremely low, requiring the design of a highly sensitive and specific assay...
October 31, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29906496/screening-and-characterization-of-a-annenix-a2-binding-aptamer-that-inhibits-the-proliferation-of-myeloma-cells
#6
Weihua Zhou, Yibin Zhang, Yayue Zeng, Minyuan Peng, Hui Li, Shuming Sun, Bianying Ma, Yanpeng Wang, Mao Ye, Jing Liu
Multiple myeloma (MM) is a malignant plasma cell disease and is considered incurable. Annexin A2 (ANXA2) is closely related to the proliferation and adhesion of MM. Using protein-SELEX, we performed a screen for aptamers that bind GST-ANXA2 from a library, and GST protein was used for negative selection. The enrichment of the ssDNA pool was monitored by filter-binding assay during selection. After nine rounds of screening and high-throughput sequencing, we obtained six candidate aptamers that bind to the ANXA2 protein...
June 12, 2018: Biochimie
https://www.readbyqxmd.com/read/29905462/the-human-biomolecular-corona-of-liposomal-doxorubicin-the-overlooked-factor-in-anticancer-drug-delivery
#7
Giulio Caracciolo, Sara Palchetti, Luca Digiacomo, Riccardo Zenezini Chiozzi, Anna Laura Capriotti, Heinz Amenitsch, Paolo Maria Tentori, Valentina Palmieri, Massimiliano Papi, Francesco Cardarelli, Daniela Pozzi, Aldo Laganà
More than twenty years after its approval by the Food and Drug Administration (FDA) liposomal doxorubicin (DOX) is still the drug of choice for the treatment of breast cancer and other conditions such as ovarian cancer and multiple myeloma. Yet, despite the efforts, liposomal DOX did not satisfy expectations at the clinical level. When liposomal drugs enter a physiological environment, their surface gets coated by a dynamic biomolecular corona (BC). The BC changes liposome's synthetic identity, providing it with a new one, referred to as 'biological identity' (size, aggregation state, and BC composition)...
June 15, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29903988/oncolytic-viruses-for-multiple-myeloma-therapy
#8
REVIEW
Christine M Calton, Kevin R Kelly, Faiz Anwer, Jennifer S Carew, Steffan T Nawrocki
Although recent treatment advances have improved outcomes for patients with multiple myeloma (MM), the disease frequently becomes refractory to current therapies. MM thus remains incurable for most patients and new therapies are urgently needed. Oncolytic viruses are a promising new class of therapeutics that provide tumor-targeted therapy by specifically infecting and replicating within cancerous cells. Oncolytic therapy yields results from both direct killing of malignant cells and induction of an anti-tumor immune response...
June 14, 2018: Cancers
https://www.readbyqxmd.com/read/29903665/-right-auricular-mass-in-a-patient-with-multiple-myeloma
#9
Francisco José Caro-Fernández, Jessica Roa-Garrido, Rosa Cardenal-Piris, Jose Francisco Díaz-Fernández
No abstract text is available yet for this article.
June 11, 2018: Archivos de Cardiología de México
https://www.readbyqxmd.com/read/29900053/quantitative-and-functional-alterations-of-6-sulfo-lacnac-dendritic-cells-in-multiple-myeloma
#10
Baptiste Lamarthée, Frédéric de Vassoigne, Florent Malard, Nicolas Stocker, Inès Boussen, Clémence Médiavilla, Ruoping Tang, Fanny Fava, Laurent Garderet, Zora Marjanovic, Eolia Brissot, Mohamad Mohty, Béatrice Gaugler
Multiple myeloma (MM) results from expansion of abnormal plasma cells in the bone marrow (BM). Previous studies have shown that monocytes play a crucial role in MM pathophysiology. A 6-sulfo LacNAc-expressing population of dendritic cells (Slan-DCs) that overlaps with intermediate and non-classical monocytes in terms of phenotype has been described. Slan-DCs represent a circulating and tissue proinflammatory myeloid population which has been shown to play a role in different cancer contexts, and which exhibits a remarkable plasticity...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899820/pre-clinical-validation-of-b-cell-maturation-antigen-bcma-as-a-target-for-t-cell-immunotherapy-of-multiple-myeloma
#11
De-Xiu Bu, Reshma Singh, Eugene E Choi, Marco Ruella, Selene Nunez-Cruz, Keith G Mansfield, Paul Bennett, Nathanial Barton, Qilong Wu, Jiquan Zhang, Yongqiang Wang, Lai Wei, Shawn Cogan, Tucker Ezell, Shree Joshi, Kellie J Latimer, Brian Granda, William R Tschantz, Regina M Young, Heather A Huet, Celeste J Richardson, Michael C Milone
Multiple myeloma has a continued need for more effective and durable therapies. B cell maturation antigen (BCMA), a plasma cell surface antigen and member of the tumor necrosis factor (TNF) receptor superfamily, is an attractive target for immunotherapy of multiple myeloma due to its high prevalence on malignant plasma cells. The current work details the pre-clinical evaluation of BCMA expression and development of a chimeric antigen receptor (CAR) targeting this antigen using a fully human single chain variable fragment (scFv)...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#12
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29899697/anti-myeloma-effects-of-icariin-are-mediated-through-the-attenuation-of-jak-stat3-dependent-signaling-cascade
#13
Young Yun Jung, Jong Hyun Lee, Dongwoo Nam, Acharan S Narula, Ojas A Namjoshi, Bruce E Blough, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
Because of the essential role of signal transducer and activator of transcription 3 (STAT3) in proliferation, anti-apoptosis, and chemoresistance of multiple myeloma (MM), we investigated whether icariin, a prenylated flavonol glycoside, inhibits both constitutive and inducible STAT3 activation in human myeloma cell lines. We noted that icariin could block constitutive STAT3 phosphorylation as well as its nuclear translocation and DNA binding ability in U266 cells. Icariin also suppressed IL-6-induced STAT3 activation through the inhibition of upstream kinases (Janus activated kinase-1 and -2, and c-Src)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29899231/smenamide-a-analogues-synthesis-and-biological-activity-on-multiple-myeloma-cells
#14
Alessia Caso, Ilaria Laurenzana, Daniela Lamorte, Stefania Trino, Germana Esposito, Vincenzo Piccialli, Valeria Costantino
Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16- epi -analogue of smenamide A and eight simplified analogues in the 16- epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16- epi -derivative is still active at nanomolar concentrations...
June 13, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29898899/linking-transcriptional-and-genetic-tumor-heterogeneity-through-allele-analysis-of-single-cell-rna-seq-data
#15
Jean Fan, Hae-Ock Lee, Soohyun Lee, Da-Eun Ryu, Semin Lee, Catherine Xue, Seok Jin Kim, Kihyun Kim, Nikolas Barkas, Peter J Park, Woong-Yang Park, Peter V Kharchenko
Characterization of intratumoral heterogeneity is critical to cancer therapy, as presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational approach called HoneyBADGER to identify copy number variation and loss-of-heterozygosity in individual cells from single-cell RNA-sequencing data...
June 13, 2018: Genome Research
https://www.readbyqxmd.com/read/29898091/cardiovascular-risk-and-use-of-conicity-index-in-patients-submitted-to-autologous-hematopoietic-stem-cell-transplantation
#16
Suelyne Rodrigues de Morais, Ana Carolina Cavalcante Viana, Ana Filomena Camacho Santos Daltro, Priscila da Silva Mendonça
OBJECTIVE: To analyze the prevalence of overweight and the use of conicity index for cardiovascular risk assessment in individuals submitted to autologous hematopoietic stem cell transplantation. METHODS: The sample comprised 91 patients of both sexes, who underwent autologous hematopoietic stem cell transplantation from September 2008 to December 2013, aged 18 years or over. To determine the nutritional profile, we collected anthropometric data on weight, height, waist circumference upon hospital admission...
June 7, 2018: Einstein
https://www.readbyqxmd.com/read/29897483/autologous-stem-cell-transplantation-for-multiple-myeloma-underutilized-but-highly-effective
#17
John P Chute
No abstract text is available yet for this article.
June 11, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29897481/association-between-autologous-stem-cell-transplant-and-survival-among-californians-with-multiple-myeloma
#18
Aaron S Rosenberg, Ann Brunson, Brian A Jonas, Theresa H M Keegan, Ted Wun
Background: Autologous hematopoietic stem cell transplant (aHSCT) is an efficacious treatment for newly diagnosed multiple myeloma patients. However, as rapid advances have resulted in other highly efficacious and less intensive therapies, the role of aHSCT has been questioned. Methods: We utilized population-based data to identify 13 494 newly diagnosed patients younger than age 80 years between 1998 and 2012. Patient characteristics of aHSCT and non-aHSCT groups were balanced using inverse probability weighting of a propensity score predicting aHSCT use...
June 11, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29895968/exosome-mediated-transfer-of-lncrunx2-as1-from-multiple-myeloma-cells-to-mscs-contributes-to-osteogenesis
#19
Bingzong Li, Hongxia Xu, Huiying Han, Sha Song, Xiaojuan Zhang, Lu Ouyang, Chen'ao Qian, Yating Hong, Yingchun Qiu, Wenqi Zhou, Moli Huang, Wenzhuo Zhuang
Multiple myeloma (MM) is characterized by the decreased osteogenic potential of mesenchymal stem cells (MSCs). Communication between cancer cells and cancer stromal cells is a driving factor in tumor progression. Understanding the myeloma-stroma interactions is critical to the development of effective strategies that can reverse bone diseases. Here we identified that bioactive lncRNA RUNX2-AS1 in myeloma cells could be packed into exosomes and transmitted to MSCs, thus repressing the osteogenesis of MSCs. RUNX2-AS1, which arises from the antisense strand of RUNX2, was enriched in MSCs derived from MM patients (MM-MSCs)...
June 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29895955/multiple-myeloma-clonal-evolution-in-homogeneously-treated-patients
#20
Jill Corre, Alice Cleynen, Sébastien Robiou du Pont, Laure Buisson, Niccolo Bolli, Michel Attal, Nikhil Munshi, Hervé Avet-Loiseau
Clonal evolution drives tumor progression, chemoresistance and relapse in cancer. Little is known about clonal selection induced by therapeutic pressure in multiple myeloma. To address this issue, we performed large targeted sequencing of bone marrow plasma cells in 43 multiple myeloma patients at diagnosis and at relapse from exactly the same intensive treatment. The most frequently mutated genes at diagnosis were KRAS (35%), NRAS (28%), DIS3 (16%), BRAF, and LRP1B (12% each). At relapse, the mutational burden was unchanged...
June 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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