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https://www.readbyqxmd.com/read/29036795/erythrocyte-deformability-and-hemorheological-profile-in-multiple-myeloma
#1
G Caimi, M Carlisi, M Montana, E Gallà, R Lo Presti, E Hopps, S Siragusa
The hemorheological profile in multiple myeloma (MM) has been extensively studied. Our investigation regarded the behavior of whole-blood viscosity, plasma viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of them had been recently diagnosed and were at the initial stage of therapy, 6 were on consolidation/conservation therapy and 5 had achieved a complete remission. On fasting venous blood we evaluated whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit×100, the ratio between plasma viscosity at low and high shear rate and the erythrocyte deformability examined by using laser diffractometry and expressed as elongation index...
October 7, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29036218/crystallographic-and-thermodynamic-characterization-of-phenylaminopyridine-bisphosphonates-binding-to-human-farnesyl-pyrophosphate-synthase
#2
Jaeok Park, Dmitry Rodionov, Joris W De Schutter, Yih-Shyan Lin, Youla S Tsantrizos, Albert M Berghuis
Human farnesyl pyrophosphate synthase (hFPPS) catalyzes the production of the 15-carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the mevalonate pathway and a well-established drug target. Notably, it was elucidated as the molecular target of nitrogen-containing bisphosphonates, a class of drugs that have been widely successful against bone resorption disorders. More recently, research has focused on the anticancer effects of these inhibitors. In order to achieve increased non-skeletal tissue exposure, we created phenylaminopyridine bisphosphonates (PNP-BPs) that have bulky hydrophobic side chains through a structure-based approach...
2017: PloS One
https://www.readbyqxmd.com/read/29034113/low-neurotoxicity-of-onx-0914-supports-the-idea-of-specific-immunoproteasome-inhibition-as-a-side-effect-limiting-therapeutic-strategy
#3
Laura von Brzezinski, Paula Säring, Peter Landgraf, Clemens Cammann, Ulrike Seifert, Daniela C Dieterich
Application of the proteasome inhibitor Bortezomib for the treatment of haematopoietic malignancies such as multiple myeloma significantly improves the average overall survival of patients. However, one of the most severe side effects is the development of peripheral neuropathies caused by neurotoxic effects of Bortezomib limiting its therapeutic efficacy. With ONX-0914 a specific inhibitor of the β5i (LMP7)-immunosubunit containing proteasomes was developed that targets exclusively the proteasome subtypes mainly expressed in immune cells including B lymphocytes as the origin of multiple myeloma...
September 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/29034060/activation-of-the-aryl-hydrocarbon-receptor-and-risk-of-lymphoma-subtypes
#4
Sonia Sanna, Giannina Satta, Marina Padoan, Sara Piro, Angela Gambelunghe, Lucia Miligi, Giovanni Maria Ferri, Corrado Magnani, Giacomo Muzi, Luigi Rigacci, Maria Giuseppina Cabras, Emanuele Angelucci, Gian Carlo Latte, Attilio Gabbas, Maria Grazia Ennas, Pierluigi Cocco
The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in several pathways known to be relevant in lymphomagenesis. Aim of our study was to explore the link between AhR activation and risk of lymphoma subtypes. We used a Dual-Luciferase Assay(®) and a luminometer to detect the activation of the luciferase gene, in HepG2 cells transfected with a specific reporter systems, by a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108), follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated in the multicentre Italian study on gene-environment interactions in lymphoma etiology (ItGxE)...
2017: International Journal of Molecular Epidemiology and Genetics
https://www.readbyqxmd.com/read/29032271/a-comparative-assessment-of-quality-of-life-in-multiple-myeloma-patients-undergoing-autologous-stem-cell-transplantation-through-an-outpatient-and-inpatient-model
#5
Massimo Martino, Sabino Ciavarella, Simona De Summa, Letteria Russo, Nicola Meliambro, Lucrezia Imbalzano, Giuseppe Alberto Gallo, Tiziana Moscato, Giuseppe Messina, Anna Ferreri, Maria Cuzzola, Giuseppe Irrera, Virginia Naso, Michele Cimminiello, Giuseppe Console, Giacomo Loseto, Stefania Tommasi, Attilio Guarini
Outpatient autologous stem cell transplantation (ASCT) has been shown to be feasible in terms of physical morbidity and mortality outcomes, but few data exist on the quality of life (QoL) impact of delivering such approach in this manner. The purpose of this prospective, observational, longitudinal, cohort study was to compare effects of inpatient (n = 76) and outpatient (n = 64) modes of care on QoL in multiple myeloma patients who underwent ASCT. Patients were treated according to their preference for inpatient or outpatient model...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29032267/long-term-follow-up-of-a-donor-versus-no-donor-comparison-in-multiple-myeloma-patients-at-first-relapse-after-failing-autologous-transplantation
#6
Francesca Patriarca, Benedetto Bruno, Hermann Einsele, Francesco Spina, Luisa Giaccone, Vittorio Montefusco, Miriam Isola, Chiara Nozzoli, Andrea Nozza, Fortunato Morabito, Paolo Corradini, Renato Fanin
We report the long-term clinical outcomes of a retrospective multicentre study that enrolled 169 multiple myeloma (MM) patients at first relapse after failing autologous stem cell transplantation (SCT). After HLA-typing at relapse, 79 patients with a suitable donor, 72 (91%) of whom eventually underwent salvage allogeneic SCT, were compared with 90 patients without a donor who were treated with multiple lines of salvage treatment with bortezomib and/or immune-modulating agents. At a median follow-up of 30 months (range 2-180) for all patients and 110 months (range 38-180) for surviving patients, 7-year progression free survival (PFS) was 18% in the donor group and 0% in the no-donor group (hazard ratio [HR] 2...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29031566/high-nrf2-expression-controls-endoplasmic-reticulum-stress-induced-apoptosis-in-multiple-myeloma
#7
Yu Sun, Amina Abdul Aziz, Kristian Bowles, Stuart Rushworth
Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation. The stress response transcription factor Nuclear factor erythroid 2 [NF-E2]-related factor 2 (NRF2) is known to be activated in MM in response to proteasome inhibitors (PI). Here, we hypothesize that the transcription factor NRF2 whose physiological role is to protect cells from reactive oxygen species via the regulation of drug metabolism and antioxidant gene plays an important role in MM cells survival and proliferation...
October 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29031125/low-protein-z-levels-in-patients-with-plasma-cell-neoplasms-are-inversely-correlated-with-il-6-levels
#8
O Gutwein, N Rahimi-Levene, K Herzog-Tzarfati, O Garach-Jehoshua, A Nagler, M Izak, M Koren-Michowitz
Patients with multiple myeloma (MM) have an increased thrombotic risk, but pathogenesis remains uncertain. Low levels of Protein Z (PZ), a vitamin K-dependent plasma protein, are associated with venous as well as arterial thrombosis. The purpose of this study was to analyze PZ levels in patients with plasma cell neoplasms. PATIENTS AND METHODS: The study consisted of 64 plasma cells neoplasm patients and 42 healthy individuals. Clinical investigations included measurement of plasma PZ and IL-6 levels...
September 25, 2017: Leukemia Research
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
#9
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/29029605/monitoring-multiple-myeloma-by-idiotype-specific-peptide-binders-of-tumor-derived-exosomes
#10
Enrico Iaccino, Selena Mimmi, Vincenzo Dattilo, Fabiola Marino, Patrizio Candeloro, Antonio Di Loria, Danilo Marimpietri, Antonio Pisano, Francesco Albano, Eleonora Vecchio, Simona Ceglia, Gaetanina Golino, Antonio Lupia, Giuseppe Fiume, Ileana Quinto, Giuseppe Scala
Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides)...
October 13, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29029544/melflufen-a-peptidase-potentiated-alkylating-agent-in-clinical-trials
#11
REVIEW
Malin Wickström, Peter Nygren, Rolf Larsson, Johan Harmenberg, Jakob Lindberg, Per Sjöberg, Markus Jerling, Fredrik Lehmann, Paul Richardson, Kenneth Anderson, Dharminder Chauhan, Joachim Gullbo
Aminopeptidases like aminopeptidase N (APN, also known as CD13) play an important role not only in normal cellular functioning but also in the development of cancer, including processes like tumor cell invasion, differentiation, proliferation, apoptosis, motility, and angiogenesis. An increased expression of APN has been described in several types of human malignancies, especially those characterized by fast-growing and aggressive phenotypes, suggesting APN as a potential therapeutic target. Melphalan flufenamide ethyl ester (melflufen, previously denoted J1) is a peptidase-potentiated alkylating agent...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029480/small-molecule-cp-31398-induces-reactive-oxygen-species-dependent-apoptosis-in-human-multiple-myeloma
#12
Yohei Arihara, Kohichi Takada, Yusuke Kamihara, Naotaka Hayasaka, Hajime Nakamura, Kazuyuki Murase, Hiroshi Ikeda, Satoshi Iyama, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Junji Kato
Reactive oxygen species (ROS) are normal byproducts of a wide variety of cellular processes. ROS have dual functional roles in cancer cell pathophysiology. At low to moderate levels, ROS act as signaling transducers to activate cell proliferation, migration, invasion, and angiogenesis. In contrast, high levels of ROS induce cell death. In multiple myeloma (MM), ROS overproduction is the trigger for apoptosis induced by several anticancer compounds, including proteasome inhibitors. However, no drugs for which oxidative stress is the main mechanism of action are currently used for treatment of MM in clinical situations...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028819/the-anti-myeloma-activity-of-bone-morphogenetic-protein-2-predominantly-relies-on-the-induction-of-growth-arrest-and-is-apoptosis-independent
#13
Charlotte Lagler, Mohamed El-Mesery, Alexander Christian Kübler, Urs Dietmar Achim Müller-Richter, Thorsten Stühmer, Joachim Nickel, Thomas Dieter Müller, Harald Wajant, Axel Seher
Multiple myeloma (MM), a malignancy of the bone marrow, is characterized by a pathological increase in antibody-producing plasma cells and an increase in immunoglobulins (plasmacytosis). In recent years, bone morphogenetic proteins (BMPs) have been reported to be activators of apoptotic cell death in neoplastic B cells in MM. Here, we use bone morphogenetic protein 2 (BMP2) to show that the "apoptotic" effect of BMPs on human neoplastic B cells is dominated by anti-proliferative activities and cell cycle arrest and is apoptosis-independent...
2017: PloS One
https://www.readbyqxmd.com/read/29027825/cost-effectiveness-of-carfilzomib-plus-dexamethasone-compared-with-bortezomib-plus-dexamethasone-for-patients-with-relapsed-or-refractory-multiple-myeloma-in-the-united-states
#14
Andrzej J Jakubowiak, Ivan Houisse, István Májer, Ágnes Benedict, Marco Campioni, Sumeet Panjabi, Sikander Ailawadhi
BACKGROUND: We assessed the economic value of carfilzomib 56 mg/m(2) and dexamethasone (Kd56) vs bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. RESEARCH DESIGN AND METHODS: Cost-effectiveness of Kd56 vs Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients...
October 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29027517/-unexpected-symptoms-of-monoclonal-gammopathy
#15
P M Smit, A C Abrahams, R G E Schutgens, N C Notermans, M C Minnema
Monoclonal gammopathy of undetermined significance (MGUS) is a common haematological disorder characterized by the presence of a monoclonal protein (M-protein). MGUS is considered an asymptomatic 'innocent' pre-malignant precursor condition of - mostly - multiple myeloma, without indication for treatment. We present three cases illustrating that MGUS can lead to serious problems. The first patient, a 51-year-old female, presented with polyneuropathy due to anti-MAG antibodies related to IgM MGUS. The second patient, a 37-year-old female, presented with proteinuria due to immunotactoid glomerulopathy caused by renal monoclonal IgG deposition associated with MGUS...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29026768/macroglossia-as-a-presenting-feature-of-multiple-myeloma
#16
Serkan Demirkan, Ekin Şavk, Alper Alp, Firuzan Kacar Doger, Gurhan Kadikoylu, Ozgur Gunduz
Macroglossia has been very rarely reported as a first clinical sign of multiple myeloma.
January 2017: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/29026685/pharmacokinetics-of-carfilzomib-in-patients-with-advanced-malignancies-and-varying-degrees-of-hepatic-impairment-an-open-label-single-arm-phase-1-study
#17
Jennifer Brown, Ruth Plummer, Todd M Bauer, Stephen Anthony, John Sarantopoulos, Filip De Vos, Mike White, Marco Schupp, Ying Ou, Ulka Vaishampayan
BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. METHODS: Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29026167/the-proteasome-inhibitor-bortezomib-attenuates-renal-fibrosis-in-mice-via-the-suppression-of-tgf-%C3%AE-1
#18
Moko Zeniya, Takayasu Mori, Naofumi Yui, Naohiro Nomura, Shintaro Mandai, Kiyoshi Isobe, Motoko Chiga, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Kidney fibrosis and fibrogenesis significantly exacerbate chronic kidney disease (CKD) progression and are essential therapeutic targets. Bortezomib (BZM) is a proteasome inhibitor used for the treatment of multiple myeloma (MM). Several studies have demonstrated that BZM attenuates renal impairment in patients with MM, although this effect is generally considered to be the result of MM remission. Recently, several studies on BZM reported anti-fibrotic effects on liver and skin in experimental animal models...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025987/preclinical-development-of-cd38-targeted-89-zr-zr-dfo-daratumumab-for-imaging-multiple-myeloma
#19
Anchal Ghai, Dolonchampa Maji, Michael Rettig, Chantiya Chanswangphuwana, John DiPersio, Walter Akers, Samuel Achilefu, Farrokh Dehdashti, Ravi Vij, Monica Shokeen
Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. Despite improvements in survival, heterogeneity in response remains a major challenge in MM. Cluster of differentiation 38 (CD38) is a type II transmembrane glycoprotein over-expressed in myeloma cells and is implicated in MM cell signaling. Daratumumab is US Food and Drug Administration approved high-affinity monoclonal antibody targeting CD38 that is clinically benefiting refractory MM patients. Here, we evaluated [(89)Zr]Zr-DFO-daratumumab positron emission tomography/computed tomography (PET/CT) imaging in MM tumor models...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29025767/monocytes-and-granulocytes-reduce-cd38-expression-levels-on-myeloma-cells-in-patients-treated-with-daratumumab
#20
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
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