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Multiple myeloma research

Zhe Sha, Helena M Schnell, Kerstin Ruoff, Alfred Goldberg
Proteasome inhibitors are used as research tools and to treat multiple myeloma, and proteasome activity is diminished in several neurodegenerative diseases. We therefore studied how cells compensate for proteasome inhibition. In 4 h, proteasome inhibitor treatment caused dramatic and selective induction of GABARAPL1 (but not other autophagy genes) and p62 , which binds ubiquitinated proteins and GABARAPL1 on autophagosomes. Knockdown of p62 or GABARAPL1 reduced cell survival upon proteasome inhibition. p62 induction requires the transcription factor nuclear factor (erythroid-derived 2)-like 1 (Nrf1), which simultaneously induces proteasome genes...
March 13, 2018: Journal of Cell Biology
Carol Keen, Julie Skilbeck, Helen Ross, Lauren Smith, Karen Collins, Joanne Dixey, Stephen Walters, Diana M Greenfield, John A Snowden, Susan Mawson
INTRODUCTION: While myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition.Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation-exercise before treatment-has been shown to be effective in other disease areas...
March 9, 2018: BMJ Open
Agnieszka Barchnicka, Małgorzata Olejniczak-Nowakowska, Karolina Krupa-Kotara, Sebastian Grosicki
Angiogenesis plays a significant role in oncogenesis, and thus it has become an attractive target for cancer treatment. It is the formation of new blood vessels that occurs physiologically as well as under pathological conditions, and may influence cancer proliferation and survival. The current therapeutic approach in oncology includes conventional chemotherapy in combination with biologically-based treatment in various perspectives, targeting not only the malignant cells, but also its microenvironment. Target treatment might be less toxic than conventional chemotherapy...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Alina Striha, A John Ashcroft, Anna Hockaday, David A Cairns, Karen Boardman, Gwen Jacques, Cathy Williams, John A Snowden, Mamta Garg, Jamie Cavenagh, Kwee Yong, Mark T Drayson, Roger Owen, Mark Cook, Gordon Cook
BACKGROUND: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response...
March 7, 2018: Trials
Charlotte Cosemans, Bénedith Oben, Ingrid Arijs, Annick Daniëls, Jeroen Declercq, Kimberly Vanhees, Guy Froyen, Brigitte Maes, Jeroen Mebis, Jean-Luc Rummens
Multiple myeloma (MM), characterized by malignant plasma cells in the bone marrow, is consistently preceded by asymptomatic premalignant stage monoclonal gammopathy of undetermined significance (MGUS). These MGUS patients have an annual risk of 1% to progress to MM. Clinical, imaging, and genomic (genetic and epigenetic) factors were identified, whose presence increased the risk of progression from MGUS to MM. In this systematic review we summarize the currently identified clinical, imaging, and genomic biomarkers suggested to increase the progression risk or shown to be differentially expressed/present between both cohorts of patients...
February 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
Eric Sanchez, Edward J Tanenbaum, Saurabh Patil, Mingjie Li, Camilia M Soof, Aleksandra Vidisheva, Gabriel N Waterman, Tara Hekmati, George Tang, Cathy S Wang, Haiming Chen, James Berenson
B-cell maturation antigen (BCMA) is a cell membrane bound tumor necrosis factor receptor family member that is expressed exclusively on late stage normal and malignant B-cells and plasma cells. Addition of two of its ligands, B-cell activating factor and a proliferation inducting ligand, to normal B-cells cause B-cell proliferation and antibody production. Serum BCMA is elevated among patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and is a prognostic and monitoring tool for these patients...
March 7, 2018: Expert Review of Molecular Diagnostics
Andrew J Cowan, Philip A Stevenson, Edward N Libby, Pamela S Becker, David G Coffey, Damian J Green, Teresa S Hyun, Jonathan R Fromm, Ajay K Gopal, Leona A Holmberg
BACKGROUND: Circulating plasma cells (CPCs) have been detected in patients with multiple myeloma (MM) at various stages of disease and associated with worse outcomes. Little data exist regarding the impact of CPCs at the time of autologous peripheral blood stem cell (PBSC) collection on outcomes, and the impact of maintenance therapy post autologous transplant (ASCT) on prognosis in patients with CPC containing collections. METHODS: All patients with MM who underwent first ASCT at Fred Hutchinson Cancer Research Center from 2012-2015 and had evaluation for CPCs at the time of PBSC collection were included in our analysis...
February 23, 2018: Biology of Blood and Marrow Transplantation
Joan Blade, Miguel Ángel Calleja, Juan José Lahuerta, José Luis Poveda, Héctor David de Paz, Luis Lizán
OBJECTIVE: To define a standard set of outcomes and the most appropriate instruments to measure them for managing newly diagnosed patients with multiple myeloma (MM). METHODS: A literature review and five discussion groups facilitated the design of two-round Delphi questionnaire. Delphi panellists (haematologists, hospital pharmacists and patients) were identified by the scientific committee, the Spanish Program of Haematology Treatments Foundation, the Spanish Society of Hospital Pharmacies and the Spanish Community of Patients with MM...
February 22, 2018: BMJ Open
Kristine A Frerichs, Noemi Anna Nagy, Pieter L Lindenbergh, Patty Bosman, Jhon Marin Soto, Marloes Broekmans, Richard W J Groen, Maria Themeli, Louise Nieuwenhuis, Claudia Stege, Inger S Nijhof, Tuna Mutis, Sonja Zweegman, Henk M Lokhorst, Niels W C J van de Donk
Multiple myeloma (MM) is generally an incurable hematological malignancy with heterogeneous overall survival rates ranging from a few months to more than 10 years. Survival is especially poor for patients who developed disease that is refractory to immunomodulatory drugs and proteasome inhibitors. Areas covered: This review will discuss the importance of CD38-targeting antibodies for the treatment of MM patients to improve their outcome. Expert commentary: Intense immuno-oncological laboratory research has resulted in the development of functionally active monoclonal antibodies against cell surface markers present on MM cells...
March 2018: Expert Review of Clinical Immunology
Jie Ying, Miaomiao Zhang, Xiaoyan Qiu, Yu Lu
The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the potential to be effective treatment strategies for diseases. Among of all of the components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs are the largest family of ubiquitin E3 ligases and they play a critical role in substrate binding...
February 15, 2018: Cancer Chemotherapy and Pharmacology
H M Mo, Q Y Wu, D Y Han, R Liu, X Ma, P Zhou, K L Xu
Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Timothy Bolt, Jörg Mahlich, Yusuke Nakamura, Masahiko Nakayama
PURPOSE: With the progress being made in the treatment of multiple myeloma and other complex cancers, a variety of clinical research and treatment options are being pursued. This study uses a discrete choice experiment (DCE) to estimate treatment characteristic preferences of hematologists in Japan. METHODS: A 2-stage process was applied within this study. The first stage is an attribute-rating exercise in which each of the full list of 21 attributes is rated on its importance by the clinicians when selecting a first-line therapy...
January 20, 2018: Clinical Therapeutics
Chang Wang, Yike Wu, Liang Zhang, Bi-Feng Liu, Yawei Lin, Xin Liu
Quantitative analysis of glycans is an emerging field in glycomic research. Herein we present a rapid and effective dual-labeling strategy, in the combination of isotopic derivatization of N-glycosylamine-based glycans by d0/d5-benzoyl chloride and methylamidation of sialic acids, to relatively quantify both neutral and sialylated N-glycans simultaneously by MALDI-MS. The derivatization efficiencies were increased by microwave-accelerated deglycosylation which not only largely reduce the time of glycoprotein deglycosylation but also inhibit the hydrolysis of intermediate glycosylamines produced by PNGase F digestion...
March 9, 2018: Analytica Chimica Acta
Catherine M Gavile, Benjamin G Barwick, Scott Newman, Paola Neri, Ajay K Nooka, Sagar Lonial, Kelvin P Lee, Lawrence H Boise
Although prognosis for patients with multiple myeloma has improved over the past decade, research toward discovery of new therapeutic avenues is important and could lead to a cure for this plasma cell malignancy. Here we show that blocking the CD28-CD86 pathway via silencing of either CD28 or CD86 leads to myeloma cell death. Inhibiting this pathway leads to downregulation of integrins and IRF4, a known myeloma survival factor. Our data also indicate that CD86, the canonical ligand in this pathway, has prosurvival activity that is dependent on its cytosolic domain...
November 28, 2017: Blood Advances
D Bazyka
After the creation of the Academy of Medical Sciences of Ukraine in 1993 the Research Center for Radiation Medicine was among the first institutions to join the Academy (fig. 1). Estab lishing the Academy was among the first steps of the independent Ukrainian government and aimed to provide a high level health care for population. It was extremely needed for the minimization of Chornobyl medical consequences. This choice was related to a growing recognition of the scientific research in fulfilling the Сenter's mission - study of the effects of low dose radiation on human body and radiation protection of the exposed population...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
Taiga Nishihori, Kenneth Shain
Although recent advances in novel treatment approaches and therapeutics have shifted the treatment landscape of multiple myeloma, it remains an incurable plasma cell malignancy. Growing knowledge of the genome and expressed genomic information characterizing the biologic behavior of multiple myeloma continues to accumulate. However, translation and incorporation of vast molecular understanding of complex tumor biology to deliver personalized and precision treatment to cure multiple myeloma have not been successful to date...
2017: International Journal of Genomics
María-Victoria Mateos, Meletios A Dimopoulos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre Crepaldi, Anna M Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Iosava, Tomoaki Fujisaki, Mamta Garg, Christopher Chiu, Jianping Wang, Robin Carson, Wendy Crist, William Deraedt, Huong Nguyen, Ming Qi, Jesus San-Miguel
BACKGROUND: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression...
February 8, 2018: New England Journal of Medicine
Shaji Kumar
Considerable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
María-Victoria Mateos, Jesús F San Miguel
Multiple myeloma is the second most frequent hematological disease. The introduction of melphalan as high-dose therapy followed by autologous hematopoietic cell transplantation (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want definitively to cure the disease. Treatment goals for transplant-eligible and non-transplant-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
Gregory M Mendez, Yash M Patel, Daniel A Ricketti, John P Gaughan, Richard D Lackman, Tae Won B Kim
BACKGROUND: Patients who undergo orthopaedic oncologic surgical procedures are at increased risk of developing a venous thromboembolism (VTE). Guidelines from surgical societies are shifting to include aspirin as a postoperative VTE prophylactic agent. The purpose of this study was to review our experience using aspirin as postoperative VTE prophylaxis for orthopaedic oncologic surgical procedures. METHODS: This study was a retrospective review of patients diagnosed with a primary malignant soft-tissue or bone tumor or metastatic carcinoma...
December 6, 2017: Journal of Bone and Joint Surgery. American Volume
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