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https://www.readbyqxmd.com/read/27919998/high-risk-of-tumor-lysis-syndrome-in-symptomatic-patients-with-multiple-myeloma-with-renal-dysfunction-treated-with-bortezomib
#1
Kana Oiwa, Mihoko Morita, Shinji Kishi, Miyuki Okura, Toshiki Tasaki, Yasufumi Matsuda, Katsunori Tai, Naoko Hosono, Takanori Ueda, Takahiro Yamauchi
BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#2
Jacalyn Rosenblatt, David Avigan
PD-1/PD-L1 pathway is a negative regulator of immune activation that is up-regulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies but single agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma specific T cells and T cell activation via PD-1/PD-L1 blockade are currently being explored...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27917682/the-preclinical-discovery-and-development-of-bortezomib-for-the-treatment-of-mantle-cell-lymphoma
#3
Richard Arkwright, Tri Minh Pham, Jeffrey A Zonder, Q Ping Dou
Introduction- Mantle cell lymphoma (MCL) is an incurable, often aggressive B-cell malignancy. Bortezomib (BTZ), the 20S proteasome inhibitor was originally developed and approved for treatment of relapsed refractory multiple myeloma, and subsequently approved for treatment of MCL. BTZ's single-agent activity induces clinical responses in approximately one-third of relapsed MCL patients. BTZ-containing combination therapies have further improved the quality and duration of clinical responses compared to standard chemotherapies in previously untreated MCL patients...
December 3, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27917370/multiple-myeloma-like-spinal-mri-findings-in-skeletal-fluorosis-an-unusual-presentation-of-fluoride-toxicity-in-human
#4
Javed Ahsan Quadri, Mohd Meraj Alam, Saba Sarwar, Ashraf Ghanai, A Shariff, Taposh K Das
Endemic fluorosis is a worldwide environmental problem due to excessive fluoride, commonly due to increased drinking water fluoride levels but sometimes due to other sources such as food with high fluoride content. In India, 21 of the 35 states are known to have health problems associated with fluoride toxicity. The present report is a case of a 50-year-old female who was seen with progressive spinal complications and a MRI of the spine suggestive of multiple myeloma. The MRI of the lumbosacral spine showed a diffuse and heterogeneous marrow signal of the lower dorsal and lumbosacral vertebrae...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27917369/management-of-multiple-myeloma-and-usage-of-bortezomib-perspective-from-india-and-ukraine
#5
Amit Garg, Mykhaylo Morgunskyy, Yogesh Belagali, Namita Gupta, Shyam Prasad Akku
Novel treatment strategies have remarkably improved the multiple myeloma (MM) patients' survival, with associated increased costs. A joint panel meet of international experts from India and Ukraine was held in New Delhi on May 19, 2016 focusing on MM management, bortezomib role, unmet medical needs, and current challenges. The health-care system for oncology in India is majorly private vs. government-based in Ukraine. In India, electrophoresis, serum-free light chain assays, bone marrow tests, and X-rays are available modes of diagnosis...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27916918/subchronic-toxicities-of-hz1006-a-hydroxamate-based-histone-deacetylase-inhibitor-in-beagle-dogs-and-sprague-dawley-rats
#6
Xiaofang Zhang, Xiaodong Zhang, Bojun Yuan, Lijun Ren, Tianbao Zhang, Guocai Lu
Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use...
November 30, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27916892/molecular-mechanisms-of-p53-deregulation-in-cancer-an-overview-in-multiple-myeloma
#7
REVIEW
Ana B Herrero, Elizabeta A Rojas, Irena Misiewicz-Krzeminska, Patryk Krzeminski, Norma C Gutiérrez
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916857/in-silico-characterization-of-mirna-and-long-non-coding-rna-interplay-in-multiple-myeloma
#8
Domenica Ronchetti, Martina Manzoni, Katia Todoerti, Antonino Neri, Luca Agnelli
The identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNA (ceRNA) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent...
November 29, 2016: Genes
https://www.readbyqxmd.com/read/27916078/-effects-of-ifosfamide-in-combination-with-pegylated-liposomal-doxorubicin-and-dexamethasone-in-the-treatment-of-relapsed-refractory-multiple-myeloma
#9
N An, M Shen, X Li, Z X Huang, S L Chen
Objective: To investigate the efficacy and adverse effects of ifosfamide in combination with pegylated liposomal doxorubicin and dexamethasone (CDD) in treating patients with relapsed/refractory multiple myeloma (MM). Methods: The clinical data of 30 relapsed/refractory MM patients treated with CDD regimen in Department of Hematology and Oncology of Beijing Chaoyang Hospital from November 2012 to November 2015 were retrospectively analyzed. The CDD treatment included ifosfamide 0.5-1.0 g/d on d1-4, pegylated liposomal doxorubicin 40-60 mg/d on d1, and dexamethasone 10-20 mg/d on d1-4...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27914161/streptococcus-agalactiae-native-valve-endocarditis-uncommon-presentation-of-multiple-myeloma
#10
Ana Pinho Oliveira, Anne Delgado, Cláudia Martins, Pedro Gama
Adults with chronic immunosuppressive conditions are at an increased risk for Streptococcus agalactiae endocarditis, which is typically characterized by acute onset, presence of large vegetations, rapid valvular destruction and frequent complications. We report a rare case of a 74 years old man presenting with fever, renal infarction, ischemic stroke and uveitis. Infective endocarditis was diagnosed and Streptococcus agalactiae was isolated in blood cultures. A multiple myeloma Ig G-K was also diagnosed. The infective endocarditis was successfully treated with a course of benzylpenicillin and gentamicin...
August 2016: Acta Médica Portuguesa
https://www.readbyqxmd.com/read/27914102/examining-temporal-effects-on-cancer-risk-in-the-international-nuclear-workers-study-inworks
#11
Robert D Daniels, Stephen J Bertke, David B Richardson, Elisabeth Cardis, Michael Gillies, Jacqueline A O'Hagan, Richard Haylock, Dominique Laurier, Klervi Leuraud, Monika Moissonnier, Isabelle Thierry-Chef, Ausrele Kesminiene, Mary K Schubauer-Berigan
The paper continues the series of publications from the International Nuclear Workers Study cohort (INWORKS) that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure...
December 3, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27913860/improved-clinical-outcomes-for-multiple-myeloma-patients-treated-at-a-single-specialty-clinic
#12
Ariana Berenson, Suzie Vardanyan, Michael David, James Wang, Nika Manik Harutyunyan, Jillian Gottlieb, Ran Halleluyan, Tanya M Spektor, Kyle A Udd, Shahrooz Eshaghian, Youram Nassir, Benjamin Eades, Regina Swift, James R Berenson
Despite recent advances made in its treatment, multiple myeloma (MM) remains an incurable B cell malignancy. Thus, the objective for treating these patients is to prolong overall survival (OS) and preserve patients' quality of life. We have analyzed data from 264 consecutive MM patients who had their initial visit between July 1, 2004 and December 1, 2014 and have received treatment in a single clinic specializing in MM. We determined their progression-free survival (PFS, OS, and 5-year OS). The PFS for frontline (n = 165 treatments), salvage (n = 980), and all treatments (n = 1145) were 13...
December 2, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#13
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#14
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913522/role-of-stem-cell-transplant-and-maintenance-therapy-in-plasma-cell-disorders
#15
Philip L McCarthy, Sarah A Holstein
Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#16
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#17
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913388/iap-antagonists-promote-phagocytosis-of-multiple-myeloma-in-vivo
#18
(no author information available yet)
The IAP antagonist LCL161 has activity against multiple myeloma cells independent of apoptosis.
December 2, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27913271/histone-deacetylases-hdac-in-physiological-and-pathological-bone-remodelling
#19
REVIEW
M D Cantley, A C W Zannettino, P M Bartold, D P Fairlie, D R Haynes
Histone deacetylases (HDACs)(2) play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi)(3) that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are currently being studied also for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes...
November 29, 2016: Bone
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#20
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
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