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https://www.readbyqxmd.com/read/29030084/characterization-and-use-of-the-novel-human-multiple-myeloma-cell-line-mc-b11-14-to-study-biological-consequences-of-crispr-mediated-loss-of-immunoglobulin-a-heavy-chain
#1
Denise K Walters, Bonnie K Arendt, Renee C Tschumper, Xiaosheng Wu, Diane F Jelinek
The genetic abnormalities underlying multiple myeloma (MM) are notoriously complex and intraclonal heterogeneity is a common disease feature. In the current study, we describe the establishment of a monoclonal IgA kappa (κ) MM cell line, designated MC-B11/14. Cytogenetic and FISH analyses of the original and relapse patient samples revealed the MM clone was non-hyperdiploid and possessed an 11;14 chromosomal translocation. The MC-B11/14 cell line, established from the relapse sample, is tetraploid and houses the t(11;14) abnormality...
October 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29027021/bortezomib-prevents-ovariectomy-induced-osteoporosis-in-mice-by-inhibiting-osteoclast-differentiation
#2
Sung-Hyun Kim, Myoung Ok Kim, Hyo Jeong Kim, Sanjiv Neupane, Hyung Joon Kim, Ji Hye Lee, Hong-Hee Kim, Jae-Young Kim, Youngkyun Lee
Bone homeostasis is achieved through coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. When the balance is skewed in favor of osteoclasts due to hormonal or inflammatory issues, pathologic bone loss occurs leading to conditions such as osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is the first in-class of proteasome inhibitors used as an anti-myeloma agent. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)-dependent osteoclast differentiation of mouse bone marrow macrophages...
October 12, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/29025767/monocytes-and-granulocytes-reduce-cd38-expression-levels-on-myeloma-cells-in-patients-treated-with-daratumumab
#3
Jakub Krejcik, Kristine A Frerichs, Inger S Nijhof, Berris van Kessel, Jeroen van Velzen, Andries C Bloem, Marloes Broekmans, Sonja Zweegman, Johan van Meerloo, René J Musters, Pino Poddighe, Richard Groen, Christopher Chiu, Torben Plesner, Henk M Lokhorst, A Kate Sasser, Tuna Mutis, Niels W C J van de Donk
PURPOSE: Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma (MM) cells. The aim of this study was to investigate the clinical implications and the underlying mechanisms of daratumumab-mediated CD38 reduction. EXPERIMENTAL DESIGN: We evaluated the effect of daratumumab alone or in combination with lenalidomide-dexamethasone, on CD38 levels of MM cells and non-tumor immune cells in the GEN501 study (daratumumab monotherapy) and the GEN503 study (daratumumab combined with lenalidomide-dexamethasone)...
October 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#4
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in MM cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase I study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28988742/chimeric-antigen-receptor-t-cell-therapy-for-hematological-malignancies-and-solid-tumors-clinical-data-to-date-current-limitations-and-perspectives
#5
REVIEW
J Gauthier, I Yakoub-Agha
Progress in our understanding of basic immunology along with the advent of bioengineering technologies have made possible the production of human T-cells expressing Chimeric Antigen Receptors (CAR T-cells). These CAR T-cells are designed to target specific antigens presented by cancer cells. Once CARs are bound to these antigens, CAR T-cells get activated and can initiate potent anti-tumor effects. We will here overview the bioengineering advances which made possible the clinical application of CAR T-cell therapy...
October 5, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28984511/interbody-distraction-and-vertebral-body-reconstruction-with-polymethylmethacrylate-for-the-treatment-of-pathological-fractures
#6
Scott L Zuckerman, Ganesh Rao, Laurence D Rhines, Ian E McCutcheon, Richard G Everson, Claudio E Tatsui
OBJECTIVE Treatment of epidural spinal cord compression (ESCC) caused by tumor includes surgical decompression and stabilization followed by postoperative radiation. In the case of severe axial loading impairment, anterior column reconstruction is indicated. The authors describe the use of interbody distraction to restore vertebral body height and correct kyphotic angulation prior to reconstruction with polymethylmethacrylate (PMMA), and report the long-term durability of such reconstruction. METHODS A single institution, prospective series of patients with ESCC undergoing single-stage decompression, anterior column reconstruction, and posterior instrumentation from 2013 to 2016 was retrospectively analyzed...
October 6, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28978241/treating-hematological-malignancies-with-cell-therapy-where-are-we-now
#7
Elisa Landoni, Barbara Savoldo
Adoptive cell therapy (ACT) is becoming an increasingly successful and widespread form of treatment for different types of cancer. Compared to chemotherapy or monoclonal antibodies, ACT is an active biological strategy, with infused immune cells featuring dynamic migration, expansion and long-term persistence properties. ACT in hematological malignancies offered the initial proof of principle of the feasibility for this innovative 'live-drug'. Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells...
October 5, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28978130/body-fat-composition-as-predictive-factor-for-treatment-response-in-patients-with-newly-diagnosed-multiple-myeloma-subgroup-analysis-of-the-prospective-gmmg-mm5-trial
#8
Jonathan P GroΔ, Johanna Nattenmüller, Stefan Hemmer, Diana Tichy, Julia Krzykalla, Hartmut Goldschmidt, Uta Bertsch, Stefan Delorme, Hans-Ulrich Kauczor, Jens Hillengass, Maximilian Merz
INTRODUCTION/BACKGROUND: Obesity is a well-known risk factor for malignant tumors and increased body mass index (BMI) is correlated to the risk of developing multiple myeloma (MM). The correlation of body fat composition with disease activity, adverse events and treatment response of MM patients has not been investigated yet. PATIENTS AND METHODS: A subgroup of 108 patients from a single institution enrolled in the prospective GMMG-MM5 trial, who received a whole-body low-dose computed tomography (WBLDCT) before induction therapy, were included in this study...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978095/melphalan-modifies-the-bone-microenvironment-by-enhancing-osteoclast-formation
#9
Ryan C Chai, Michelle M McDonald, Rachael L Terry, Nataša Kovačić, Jenny M Down, Jessica A Pettitt, Sindhu T Mohanty, Shruti Shah, Gholamreza Haffari, Jiake Xu, Matthew T Gillespie, Michael J Rogers, John T Price, Peter I Croucher, Julian M W Quinn
Melphalan is a cytotoxic chemotherapy used to treat patients with multiple myeloma (MM). Bone resorption by osteoclasts, by remodeling the bone surface, can reactivate dormant MM cells held in the endosteal niche to promote tumor development. Dormant MM cells can be reactivated after melphalan treatment; however, it is unclear whether melphalan treatment increases osteoclast formation to modify the endosteal niche. Melphalan treatment of mice for 14 days decreased bone volume and the endosteal bone surface, and this was associated with increases in osteoclast numbers...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967897/donor-t-cell-responses-and-disease-progression-patterns-of-multiple-myeloma
#10
M Eefting, L C de Wreede, P A Von dem Borne, C J M Halkes, S Kersting, E W A Marijt, H Putter, H Veelken, J Schetelig, J H F Falkenburg
Donor T-cells transferred after allogeneic stem cell transplantation (alloSCT) can result in long-term disease control in myeloma by the graft-versus-myeloma (GvM) effect. However, T-cell therapy may show differential effectiveness against bone marrow (BM) infiltration and focal myeloma lesions resulting in different control and progression patterns. Outcomes of 43 myeloma patients who underwent T-cell-depleted alloSCT with scheduled donor lymphocyte infusion (DLI) were analyzed with respect to diffuse BM infiltration and focal progression...
October 2, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28962646/pil6-trail-engineered-umbilical-cord-mesenchymal-stromal-stem-cells-are-highly-cytotoxic-for-myeloma-cells-both-in-vitro-and-in-vivo
#11
Paola Cafforio, Luigi Viggiano, Francesco Mannavola, Eleonora Pellè, Concetta Caporusso, Eugenio Maiorano, Claudia Felici, Francesco Silvestris
BACKGROUND: Mesenchymal/stromal stem cells (MSCs) are favorably regarded in anti-cancer cytotherapies for their spontaneous chemotaxis toward inflammatory and tumor environments associated with an intrinsic cytotoxicity against tumor cells. Placenta-derived or TRAIL-engineered adipose MSCs have been shown to exert anti-tumor activity in both in-vitro and in-vivo models of multiple myeloma (MM) while TRAIL-transduced umbilical cord (UC)-MSCs appear efficient inducers of apoptosis in a few solid tumors...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28961609/dcone-as-an-allogeneic-cell-based-vaccine-for-multiple-myeloma
#12
Rebecca Karp Leaf, Dina Stroopinsky, Athalia R Pyzer, Ada M Kruisbeek, Sandra van Wetering, Abigail Washington, Adam Ephraim, Leandra Cole, Adam Morin, Salvia Jain, Myrna R Nahas, Arik Apel, Jon Arnason, Ayad Hamdan, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is characterized by progressive immune dysregulation, loss of myeloma-specific immunity, and an immunosuppressive milieu that fosters disease growth and immune escape. Accordingly, cancer vaccines that reverse tumor-associated immune suppression represent a promising therapeutic avenue of investigation. We examined the potential of an allogeneic cellular vaccine to generate immune responses against MM tumor cells. The DCOne vaccine is comprised of a human myeloid leukemia cell line differentiated into a fully functional dendritic cell, expressing a range of tumor-associated antigens that are also known targets in MM...
November 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28958644/immunoglobulin-therapy-in-hematologic-neoplasms-and-after-hematopoietic-cell-transplantation
#13
REVIEW
Masumi Ueda, Melvin Berger, Robert Peter Gale, Hillard M Lazarus
Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer...
September 19, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28951562/a-compound-chimeric-antigen-receptor-strategy-for-targeting-multiple-myeloma
#14
K H Chen, M Wada, K G Pinz, H Liu, X Shuai, X Chen, L E Yan, J C Petrov, H Salman, L Senzel, E L H Leung, X Jiang, Y Ma
Current clinical outcomes using CARs against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen positive or negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing 2 complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1...
September 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28946631/alcohol-misuse-link-to-poems-syndrome-in-a-patient
#15
John Neary, Susan E Goodwin, Lawrence B Cohen, Manuela G Neuman
Previously called Crow-Fukase syndrome, POEMS syndrome is characterized by poly-neuropathy, osteo-sclerotic myeloma, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Extremely elevated levels of serum vascular endothelial growth factor (VEGF) are characteristic of the syndrome. Chronic hepatitis B (HBV) and C (HCV) infections can also be present in POEMS. The pathogenesis of the syndrome is not well understood. The link between chronic alcohol consumption and this malignant condition has not been reported until now...
September 23, 2017: Cancers
https://www.readbyqxmd.com/read/28945825/prognostic-value-of-sequencing-based-minimal-residual-disease-detection-in-patients-with-multiple-myeloma-who-underwent-autologous-stem-cell-transplantation
#16
H Takamatsu, N Takezako, J Zheng, M Moorhead, V E H Carlton, K A Kong, R Murata, S Ito, T Miyamoto, K Yokoyama, K Matsue, T Sato, T Kurokawa, H Yagi, Y Terasaki, K Ohata, M Matsumoto, T Yoshida, M Faham, S Nakao
Background: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. Patients and methods: We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR)...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28944848/cmip-is-oncogenic-in-human-gastric-cancer-cells
#17
Jianlin Zhang, Jin Huang, Xingyu Wang, Weidong Chen, Qinqing Tang, Maoyong Fang, Yeben Qian
Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma...
September 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28933361/lysosomal-storage-disorders-and-malignancy
#18
REVIEW
Gregory M Pastores, Derralynn A Hughes
Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933264/from-a-better-understanding-of-the-mechanisms-of-action-of-histone-deacetylases-inhibitors-to-the-progress-of-the-treatment-of-malignant-lymphomas-and-plasma-cell-myeloma
#19
Romeo-Gabriel Mihăilă
BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
September 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#20
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
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