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Treatment of myeloma

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https://www.readbyqxmd.com/read/28318212/multiple-myeloma-diagnosis-and-treatment
#1
Thomas C Michels, Keith E Petersen
Multiple myeloma accounts for 1.6% of all cancer cases and approximately 10% of hematologic malignancies in the United States. In 2015, an estimated 28,850 new cases of multiple myeloma were diagnosed in the United States, and the disease caused more than 11,000 deaths. Patients older than 65 years account for 85% of those diagnosed with multiple myeloma, and there is a twofold increased incidence in blacks compared with whites. Patients may present with bone pain or with symptoms that are often nonspecific, such as nausea, vomiting, malaise, weakness, recurrent infections, and weight loss...
March 15, 2017: American Family Physician
https://www.readbyqxmd.com/read/28317148/bortezomib-induced-peripheral-neuropathy-a-genome-wide-association-study-on-multiple-myeloma-patients
#2
Chiara Campo, Miguel Inacio da Silva Filho, Niels Weinhold, Seyed Hamidreza Mahmoudpour, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment...
March 20, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28317082/current-review-on-high-risk-multiple-myeloma
#3
REVIEW
Henry S H Chan, Christine I Chen, Donna E Reece
PURPOSE OF REVIEW: New risk stratification systems and treatment strategies have been introduced in recent years. We aim to provide an overview of these recent changes and summarise these data in a concise article that would be useful for clinicians. RECENT FINDINGS: Apart from clinical stage, disease genetics are now recognised as important prognostic risk factors, and various new cytogenetic changes with negative prognostic impact have been identified. New technologies such as minimal residual disease detection are also playing an important role in prognostic assessment...
March 20, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28317080/the-critical-role-of-imaging-in-the-management-of-multiple-myeloma
#4
REVIEW
Shahzad Raza, Siyang Leng, Suzanne Lentzsch
Multiple myeloma (MM) is characterized by abnormal proliferation of plasma cells in the bone marrow leading to symptoms of anemia, renal failure, hypercalcemia, and bone lesions. Bone imaging is critical for the diagnosis, staging, assessment for the presence and extent of bone lesions, and initial treatment of MM. Skeletal survey is the preferred initial imaging modality due to its availability and low cost. However, it has poor sensitivity and patients with occult myeloma may escape detection, delaying their diagnosis and treatment...
March 20, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28316065/identification-of-key-genes-and-construction-of-microrna-mrna-regulatory-networks-in-multiple-myeloma-by-integrated-multiple-geo-datasets-using-bioinformatics-analysis
#5
Hongyu Gao, Huihan Wang, Wei Yang
Multiple myeloma (MM) is a common hematological malignancy. To identify key genes and microRNAs in MM, we downloaded two gene expression profiles (GSE16558 and GSE47552) and two microRNA expression profiles (GSE17498 and GSE16558) from the Gene Expression Omnibus (GEO) database. A total of 596 differentially expressed genes (DEGs) and 39 differentially expressed microRNAs (DEMs) were screened out. Pathway analysis showed that upregulated genes were mainly enriched in the "B cell receptor signaling pathway", "Cell cycle" and "NF-kappa B signaling pathway", whereas downregulated genes were mainly enriched in the "Ribosome", "FoxO signaling pathway" and "p53 signaling pathway"...
March 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28315528/steroid-associated-side-effects-a-symptom-management-update-on-multiple-myeloma-treatment%C3%A2
#6
Tracy King, Beth Faiman
BACKGROUND: One constant and relatively unchanged aspect of treatment of multiple myeloma (MM) is the use of glucocorticosteroids, or steroids, which can cause a wide range of adverse side effects and harm patients' quality of life.
. OBJECTIVES: The objective of this study was to provide updated recommendations on the management of steroid-associated side effects in patients with MM.
. METHODS: A study of steroid-associated side effects in MM treatment regimens was reviewed to provide updated recommendations to healthcare professionals...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28315070/mechanisms-of-resistance-in-multiple-myeloma
#7
Athanasios Papadas, Fotis Asimakopoulos
Multiple myeloma (MM) is an incurable hematopoietic cancer that is characterized by malignant plasma cell infiltration of the bone marrow and/or extramedullary sites. Multi-modality approaches including "novel agents," traditional chemotherapy, and/or stem cell transplantation are used in MM therapy. Drug resistance, however, ultimately develops and the disease remains incurable for the vast majority of patients. In this chapter, we review both tumor cell-autonomous and non-autonomous (microenvironment-dependent) mechanisms of drug resistance...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28304402/prospective-longitudinal-study-on-quality-of-life-in-relapsed-refractory-multiple-myeloma-patients-receiving-second-or-third-line-lenalidomide-or-bortezomib-treatment
#8
X Leleu, C Kyriakou, I Vande Broek, P Murphy, P Bacon, P Lewis, H Gilet, B Arnould, M T Petrucci
Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients' health-related quality of life (HRQoL) in clinical studies. HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more patients with dialysis required)...
March 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28303902/ms4a4a-a-novel-cell-surface-marker-for-m2-macrophages-and-plasma-cells
#9
Ratna Sanyal, Maria J Polyak, Jonathan Zuccolo, Mandip Puri, Lili Deng, Luc Roberts, Ania Zuba, Jan Storek, Joanne M Luider, Ellen M Sundberg, Adnan Mansoor, Eva Baigorri, Michael P Chu, Andrew R Belch, Linda M Pilarski, Julie P Deans
MS4A4A is a member of the membrane-spanning, 4 domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcRβ (MS4A2) and Htm4 (MS4A3). Like the first three members of this family, transcription of MS4A4A appears to be limited to hematopoietic cells. To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets we generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood we found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes...
March 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28301380/nitroxoline-shows-antimyeloma-activity-by-targeting-the-trim25-p53-axle
#10
Hongwu Mao, Yanyun Du, Zubin Zhang, Biyin Cao, Jun Zhao, Haibin Zhou, Xinliang Mao
The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28299525/poems-syndrome-an-enigma
#11
REVIEW
Rahma Warsame, Uday Yanamandra, Prashant Kapoor
POEMS syndrome is a paraneoplastic disorder secondary to an underlying plasma cell dyscrasia. By definition, all patients with POEMS syndrome must display polyneuropathy and monoclonal plasma cell disorder. In addition, at least one major criterion (Castleman's disease, sclerotic bone lesions, or vascular endothelial growth factor elevation) and one minor criterion (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis, or polycythemia) are required for diagnosis...
March 15, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28295507/crocin-suppresses-constitutively-active-stat3-through-induction-of-protein-tyrosine-phosphatase-shp-1
#12
Buyun Kim, Ki Yong Lee, Byoungduck Park
The aim of the present study is to investigate the effect of a natural compound crocin, one of the active components of saffron, on human multiple myeloma cells. Crocin effectively suppressed constitutive STAT3 activation, translocation of STAT3 to the nucleus, and its target gene expression. The suppression of STAT3 was mediated through the inhibition of activation of protein tyrosine kinases JAK1, JAK2 and c-Src. We found that crocin induced the expression of SHP-1, a tyrosine protein phosphatase, and pervanadate treatment reversed the crocin-induced downregulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase...
March 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28292432/antibodies-create-killer-bonds-in-myeloma
#13
Marta Chesi, Rafael Fonseca
In this issue of Cancer Cell, Li et al. and Seckinger et al. describe promising results of two T-cell-dependent bi-specific antibodies for the treatment of multiple myeloma: one targets FcRH5 expressed on B cells, whereas the other targets the B cell maturation antigen expressed on plasma cells.
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28291404/outcomes-and-effectiveness-of-posterior-occipitocervical-fusion-for-suboccipital-spinal-metastases
#14
Panya Luksanapruksa, Jacob M Buchowski, Neill M Wright, Frank H Valone, Colleen Peters, David B Bumpass
OBJECTIVE The incidence of suboccipital spinal metastases is rare but has increased given cancer patients' longer life expectancies. Operative treatment in this region is often challenging because of limited fixation points due to tumor lysis, as well as adjacent neural and vascular anatomy. Few studies have reported on this population of cancer patients. The purpose of this study was to evaluate clinical outcomes and complications of patients with suboccipital spinal metastases who had undergone posterior occipitocervical fixation...
February 24, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28290121/population-pharmacokinetic-analysis-of-ixazomib-an-oral-proteasome-inhibitor-including-data-from-the-phase-iii-tourmaline-mm1-study-to-inform-labelling
#15
Neeraj Gupta, Paul M Diderichsen, Michael J Hanley, Deborah Berg, Helgi van de Velde, R Donald Harvey, Karthik Venkatakrishnan
Ixazomib is an oral proteasome inhibitor, approved in USA, Canada, Australia and Europe in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. We report a population pharmacokinetic model-based analysis for ixazomib that was pivotal in describing the clinical pharmacokinetics of ixazomib, to inform product labelling. Plasma concentration-time data were collected from 755 patients who received oral or intravenous ixazomib in once- or twice-weekly schedules in ten trials, including the global phase III TOURMALINE-MM1 study...
March 13, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28288323/anti-angiogenic-and-anti-multiple-myeloma-effects-of-oprozomib-opz-alone-and-in-combination-with-pomalidomide-pom-and-or-dexamethasone-dex
#16
REVIEW
Eric Sanchez, Mingjie Li, Cathy S Wang, George Tang, Abigail Gillespie, Haiming Chen, James R Berenson
Oprozomib (OPZ or ONYX 0912) is an irreversible, orally administered proteasome inhibitor (PI) and an analog of carfilzomib. We set out to determine the anti-angiogenic effect of OPZ using the choriollantoic membrane/feather bud (CAM/FB) model and its anti-MM effects using MM xenograft models (LAGκ-1A, LAGλ-1). OPZ significantly reduced blood vessel formation, endothelial gene and protein expression using the CAM/FB assay. In vivo, we determined the anti-MM effects of OPZ, dexamethasone (Dex) and pomalidomide (Pom) and showed that the combinations of two drugs (OPZ+Dex or OPZ+Pom) showed marked anti-MM effects when compared to monotherapy...
March 6, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28286629/impact-of-crab-symptoms-in-survival-of-patients-with-symptomatic-myeloma-in-novel-agent-era
#17
Aya Nakaya, Shinya Fujita, Atsushi Satake, Takahisa Nakanishi, Yoshiko Azuma, Yukie Tsubokura, Masaaki Hotta, Hideaki Yoshimura, Kazuyoshi Ishii, Tomoki Ito, Shosaku Nomura
The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents...
February 23, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28286198/in-hospital-mortality-and-post-transplant-complications-in-elderly-multiple-myeloma-patients-undergoing-autologous-hematopoietic-stem-cell-transplantation-a-population-based-study
#18
Larysa Sanchez, Michael Sylvester, Ricardo Parrondo, Veronica Mariotti, Jean Anderson Eloy, Victor T Chang
Autologous hematopoietic stem cell transplantation (auto-HSCT) has improved survival in patients with multiple myeloma (MM) and is increasingly used in elderly patients. The aim of this study was to characterize and compare in-hospital complications and mortality after auto-HSCT in younger (< age 65) vs. elderly (≥ age 65) MM patients utilizing the Nationwide Inpatient Sample (NIS). Over a three-year period (2008-2010), 2209 patients with MM were admitted to U.S. Hospitals for auto-HSCT. The median age was 59 years, with 1650 patients (74...
March 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28285807/a-brighter-side-to-thalidomide-its-potential-use-in-immunological-disorders
#19
REVIEW
David Millrine, Tadamitsu Kishimoto
Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD)...
March 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28285435/allogeneic-hematopoietic-cell-transplantation-for-myeloma-when-and-in-whom-does-it-work
#20
REVIEW
Qaiser Bashir, Muzaffar H Qazilbash
The growing list of available therapies for patients with multiple myeloma has resulted in tremendously high response rates and prolonged survival. However, the cure remains elusive. A continued effort at developing strategies to utilize all available treatment modalities in the most effective manner is needed. Allogeneic hematopoietic cell transplantation (allo-HCT) is a robust platform, associated with high response rates, and provides a unique foundation on which immune therapies and novel agents can be employed to improve clinical outcomes...
March 11, 2017: Current Hematologic Malignancy Reports
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