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https://www.readbyqxmd.com/read/28918604/symptom-experience-of-multiple-myeloma-symmex-patients-treated-with-autologous-stem-cell-transplantation-following-high-dose-melphalan-a-descriptive-longitudinal-study
#1
Matthias Naegele, Monika Kirsch, Gabriele Ihorst, Katharina Fierz, Monika Engelhardt, Sabina De Geest
PURPOSE: High-dose melphalan and autologous stem cell transplantation (ASCT) are associated with high symptom burden. This study aimed to explore multiple myeloma (MM) patients' experience of symptom frequency, intensity, and distress during therapy. METHODS: This descriptive longitudinal study enrolled 29 MM patients who completed the 43-item PROVIVO questionnaire, measuring symptom experience across the dimensions of frequency, intensity, and distress at four assessment points: hospital admission (T0), leucocyte nadir (T1), discharge (T2), and 30 days post discharge (T3)...
September 16, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28916410/kinetic-stability-and-sequence-structure-studies-of-urine-derived-bence-jones-proteins-from-multiple-myeloma-and-light-chain-amyloidosis-patients
#2
Luis M Blancas-Mejía, Emily B Martin, Angela Williams, Jonathan S Wall, Marina Ramirez-Alvarado
It is now accepted that the ability of a protein to form amyloid fibrils could be associated both kinetic and thermodynamic protein folding parameters. A recent study from our laboratory using recombinant full-length (encompassing the variable and constant domain) immunoglobulin light chains found a strong kinetic control of the protein unfolding for these proteins. In this study, we are extending our analysis by using urine-derived Bence Jones proteins (BJPs) from five patients with light chain (AL) amyloidosis and four patients with multiple myeloma (MM)...
September 1, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28916338/structure-activity-relationship-study-of-small-molecule-inhibitors-of-the-deptor-mtor-interaction
#3
Jihye Lee, Yijiang Shi, Mario Vega, Yonghui Yang, Joseph Gera, Michael E Jung, Alan Lichtenstein
DEPTOR is a 48kDa protein that binds to mTOR and inhibits this kinase within mTORC1 and mTORC2 complexes. Over-expression of DEPTOR specifically occurs in the multiple myeloma (MM) tumor model and DEPTOR knockdown is cytotoxic to MM cells, suggesting it is a potential therapeutic target. Since mTORC1 paralysis protects MM cells against DEPTOR knockdown, it indicates that the protein-protein interaction between DEPTOR and mTOR is key to MM viability vs death. In a previous study, we used a yeast two-hybrid screen of a small inhibitor library to identify a compound that inhibited DEPTOR/mTOR binding in yeast...
September 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#4
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C - X - C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
September 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28915637/btk-suppresses-myeloma-cellular-senescence-through-activating-akt-p27-rb-signaling
#5
Chunyan Gu, Hailin Peng, Yue Lu, Hongbao Yang, Zhidan Tian, Gang Yin, Wen Zhang, Sicheng Lu, Yi Zhang, Ye Yang
We previously explored the role of BTK in maintaining multiple myeloma stem cells (MMSCs) self-renewal and drug-resistance. Here we investigated the elevation of BTK suppressing MM cellular senescence, a state of irreversible cellular growth arrest. We firstly discovered that an increased expression of BTK in MM samples compared to normal controls by immunohistochemistry (IHC), and significant chromosomal gain in primary samples. In addition, BTK high-expressing MM patients are associated with poor outcome in both Total Therapy 2 (TT2) and TT3 cohorts...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915615/expression-of-cd38-in-myeloma-bone-niche-a-rational-basis-for-the-use-of-anti-cd38-immunotherapy-to-inhibit-osteoclast-formation
#6
Federica Costa, Denise Toscani, Antonella Chillemi, Valeria Quarona, Marina Bolzoni, Valentina Marchica, Rosanna Vescovini, Cristina Mancini, Eugenia Martella, Nicoletta Campanini, Chiara Schifano, Sabrina Bonomini, Fabrizio Accardi, Alberto L Horenstein, Franco Aversa, Fabio Malavasi, Nicola Giuliani
It is known that multiple myeloma (MM) cells express CD38 and that a recently developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma killing. However, the expression of CD38 and other functionally related ectoenzymes within the MM bone niche and the potential effects of Daratumumab on bone cells are still unknown. This study firstly defines by flow cytometry and immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of patients with MM and indolent monoclonal gammopathies...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915594/identification-of-precision-treatment-strategies-for-relapsed-refractory-multiple-myeloma-by-functional-drug-sensitivity-testing
#7
Muntasir Mamun Majumder, Raija Silvennoinen, Pekka Anttila, David Tamborero, Samuli Eldfors, Bhagwan Yadav, Riikka Karjalainen, Heikki Kuusanmäki, Juha Lievonen, Alun Parsons, Minna Suvela, Esa Jantunen, Kimmo Porkka, Caroline A Heckman
Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915587/expression-and-release-of-glucose-regulated-protein-78-grp78-in-multiple-myeloma
#8
Normann Steiner, Bojana Borjan, Roman Hajek, Karin Jöhrer, Georg Göbel, Wolfgang Willenbacher, Johann Kern, Eberhard Gunsilius, Gerold Untergasser
INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914853/-uromodulin-gene-polymorphisms-in-patients-with-cast-nephropathy-in-multiple-myeloma
#9
I G Rekhtina, L P Mendeleeva, B V Biderman, M V Solovyev, A B Sudarikov
AIM: To investigate the nature of mutations in exons 4 and 5 of the uromodulin (UM) gene, including in the area encoding the domain of 8 cysteines (D8C), in patients with multiple myeloma (MM) with the secretion of monoclonal light chains (LC) in cast nephropathy (CN) and without kidney injury. SUBJECTS AND METHODS: The investigation enrolled 24 patients in MM remission, who were observed to have monoclonal LC secretion at onset. Group 1 included 14 patients with CN; Group 2 consisted of 10 patients with normal renal function (a comparison group)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28914153/cardiotoxicity-with-carfilzomib-at-doses-greater-than-27%C3%A2-mg-m-2-a-case-series
#10
Gee Youn Kim, Tania Ahuja, John Papadopoulos, Frank Cirrone
Carfilzomib is a second-generation proteasome inhibitor that irreversibly inhibits chymotrypsin-like (CT-L) activities of the proteasome, and is indicated for relapsed or refractory multiple myeloma. Cardiotoxicity is a well-established adverse effect of carfilzomib. The extent of cardiac toxicity in the literature spans anywhere from palpitations to cardiac arrest, with the most commonly reported manifestation being new-onset or worsening heart failure. A pre-clinical study of the pharmacokinetics and pharmacodynamics of carfilzomib given via intravenous bolus or 30-minute infusion in rats showed that carfilzomib can strongly induce apoptosis and potently damage cardiac myocytes at clinically relevant concentrations...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28913153/quantitative-analysis-of-18-f-naf-dynamic-pet-ct-cannot-differentiate-malignant-from-benign-lesions-in-multiple-myeloma
#11
Christos Sachpekidis, Jens Hillengass, Hartmut Goldschmidt, Hoda Anwar, Uwe Haberkorn, Antonia Dimitrakopoulou-Strauss
A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical (18)F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of (18)F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with (18)F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD)...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28912253/physiologically-based-pharmacokinetic-model-predictions-of-panobinostat-lbh589-as-a-victim-and-perpetrator-of-drug-drug-interactions
#12
Heidi J Einolf, Wen Lin, Christina S Won, Lai Wang, Helen Gu, Dung Yu Chun, Handan He, James B Mangold
Panobinostat (Farydak®) is an orally active hydroxamic acid derived histone deacetylase inhibitor for the treatment of relapsed/refractory multiple myeloma. Based upon recombinant cytochrome P450 (CYP) kinetic analyses in vitro, panobinostat oxidative metabolism in human liver microsomes was found to be primarily mediated by CYP3A4 with lower contributions by CYP2D6 and CYP2C19. Panobinostat was also shown to be an in vitro reversible and time-dependent inhibitor of CYP3A4/5, and a reversible inhibitor of CYP2D6 and CYP2C19...
September 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28911826/immunoproteasome-selective-and-non-selective-inhibitors-a-promising-approach-for-the-treatment-of-multiple-myeloma
#13
REVIEW
Roberta Ettari, Maria Zappalà, Silvana Grasso, Caterina Musolino, Vanessa Innao, Alessandro Allegra
The ubiquitin-proteasome system (UPS) is the major non-lysosomal proteolytic system for the degradation of abnormal or damaged proteins no longer required. The proteasome is involved in degradation of numerous proteins which regulate the cell cycle, indicating a role in controlling cell proliferation and maintaining cell survival. Defects in the UPS can lead to anarchic cell proliferation and to tumor development. For these reasons UPS inhibition has become a significant new strategy for drug development in cancer treatment...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28906482/real-life-experience-with-bortezomib-based-regimens-in-elderly-comorbid-patients-with-newly-diagnosed-multiple-myeloma-polish-retrospective-multicenter-analysis
#14
Iwona Hus, Adam Walter-Croneck, Anna Masternak, Artur Jurczyszyn, Lidia Usnarska-Zubkiewicz, Łukasz Bołkun, Agnieszka Druzd-Sitek, Marcin Rymko, Jadwiga Łętowska, Ewa Lech-Marańda, Marcin Pasiarski, Anna Dmoszyńska
INTRODUCTION    Bortezomib was the first proteasome inhibitor approved in multiple myeloma therapy, initially for resistant/relapsed disease. Currently, VMP (bortezomib, melphalan, prednisone) is one of standard regimens recommended in a first line therapy for patients with multiple myeloma ineligible for high-dose chemotherapy/ autotransplantation (HDT/autoSCT) basing on the results of phase 3 clinical trial by Miguel et al that demonstrated its superiority to MP protocol.  OBJECTIVES    Patients participating in clinical trials are highly selected populations, so observations from clinical practice might provide important information for medical practitioners...
September 14, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28906275/vv-ecmo-assisted-high-risk-endobronchial-stenting-as-rescue-for-asphyxiating-mediastinal-mass
#15
Brandon T Nokes, Laszlo Vaszar, Jama Jahanyar, Karen L Swanson
The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) has traditionally been limited to a narrow set of clinical circumstances, such as acute hypoxic respiratory failure, submassive pulmonary embolism, and cardiopulmonary collapse. Within the pediatric population, there have been cases of VV-ECMO in the context of extrinsic airway compression by a mediastinal mass, typically in the setting of either a lymphoma or germ cell tumors. However, the use of VV-ECMO for adults with extrinsic airway compression is comparatively limited...
September 12, 2017: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/28905994/microrna-324-5p-regulates-stemness-pathogenesis-and-sensitivity-to-bortezomib-in-multiple-myeloma-cells-by-targeting-hedgehog-signaling
#16
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of Hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28905189/bortezomib-and-low-dose-dexamethasone-with-or-without-continuous-low-dose-oral-cyclophosphamide-for-primary-refractory-or-relapsed-multiple-myeloma-a-randomized-phase-iii-study
#17
Martin Kropff, Martin Vogel, Guido Bisping, Rudolf Schlag, Rudolf Weide, Wolfgang Knauf, Heinrich Fiechtner, Georgi Kojouharoff, Stephan Kremers, Wolfgang E Berdel
This phase III, open-label, randomized, controlled study aimed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma. Patients were randomized 1:1 to receive up to eight 3-week cycles of bortezomib (1.3 mg/m(2)) and dexamethasone (20 mg; VD; n = 48) or bortezomib-dexamethasone plus oral cyclophosphamide (50 mg; VCD; n = 48). Median time to progression (primary endpoint) was slightly longer in the VD versus VCD group (12...
September 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28905085/-focal-lesions-in-whole-body-mri-in-multiple-myeloma-quantification-of-tumor-mass-and-correlation-with-disease-related-parameters-and-prognosis
#18
S C Brandelik, J Krzykalla, T Hielscher, J Hillengass, J K Kloth, H U Kauczor, M A Weber
BACKGROUND AND OBJECTIVES: In this study, we evaluated methods of quantification of tumor mass in whole-body MRI (wb-MRI) in multiple myeloma and correlated these with disease-related parameters in serum and bone marrow. MATERIALS AND METHODS: We retrospectively evaluated wb-MRIs of 52 patients with focal infiltration pattern and a total of 700 focal lesions (subsequently called lesions). We determined the longest diameter (LD), the segmented volume (SV), and the morphology (spherical or non-spherical)...
September 13, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28904172/fda-approval-summary-daratumumab-for-treatment-of-multiple-myeloma-after-one-prior-therapy
#19
Vishal Bhatnagar, Nicole J Gormley, Lola Luo, Yuan Li Shen, Rajeshwari Sridhara, Sriram Subramaniam, Guoxiang Shen, Lian Ma, Stacy Shord, Kirsten B Goldberg, Ann T Farrell, Amy E McKee, Richard Pazdur
On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone...
September 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28903971/extracellular-s100a9-protein-in-bone-marrow-supports-multiple-myeloma-survival-by-stimulating-angiogenesis-and-cytokine-secretion
#20
Kim De Veirman, Nathan De Beule, Ken Maes, Eline Menu, Elke De Bruyne, Hendrik De Raeve, Karel Fostier, Jerome Moreaux, Alboukadel Kassambara, Dirk Hose, Roy Heusschen, Helena Eriksson, Karin Vanderkerken, Els Van Valckenborgh
Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples...
September 13, 2017: Cancer Immunology Research
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