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https://www.readbyqxmd.com/read/29456035/a-comparison-of-the-efficacy-of-immunomodulatory-containing-regimens-in-relapsed-refractory-multiple-myeloma-a-network-meta-analysis
#1
Meletios Athanasios Dimopoulos, Jonathan L Kaufman, Darrell White, Gordon Cook, Maria Rizzo, Yingxin Xu, Kyle Fahrbach, Maren Gaudig, Mary Slavcev, Lindsay Dearden, Annette Lam
BACKGROUND: Previous network meta-analyses combined studies of immunomodulatory drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing regimens differ from those treated with IMiD-free regimens, especially relating to treatment history, which is an important treatment-effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options...
January 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29455667/role-of-non-receptor-tyrosine-kinases-in-hematological-malignances-and-its-targeting-by-natural-products
#2
REVIEW
Kodappully S Siveen, Kirti S Prabhu, Iman W Achkar, Shilpa Kuttikrishnan, Sunitha Shyam, Abdul Q Khan, Maysaloun Merhi, Said Dermime, Shahab Uddin
Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455093/quantitative-determination-of-a-potent-geranylgeranyl-diphosphate-synthase-inhibitor-using-lc-ms-ms-derivatization-and-application
#3
Yashpal S Chhonker, Staci L Haney, Robert A Matthiesen, David F Wiemer, Sarah A Holstein, Daryl J Murry
An isomeric mixture of homogeranyl/homoneryl triazole bisphosphonates (VSW1198) has previously been shown to be a potent inhibitor of geranylgeranyl diphosphate (GGDP) synthase (GGDPS) and of therapeutic interest for the treatment of multiple myeloma. We have developed and validated a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitation of both the E- and Z- isomers of VSW1198 in cell culture media, mouse plasma and tissues. VSW1198 and internal standard are extracted from the bio-matrices by solid-phase extraction, followed by derivatization using trimethylsilyldiazomethane...
February 6, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29454645/characterization-of-cd4-t-cell-mediated-cytotoxicity-in-patients-with-multiple-myeloma
#4
Xiaole Zhang, Lei Gao, Kai Meng, Chunting Han, Qiang Li, Zhenjun Feng, Lei Chen
Multiple myeloma (MM) is an incurable cancer characterized by the development of malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a major player in antitumor immunity, but in MM patients, the CD8 T cells displayed senescence markers and were functionally impaired. To investigate whether cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the frequency and function of naturally occurring cytotoxic CD4 T cells in MM patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-, and perforin-expressing CD4 T cells, and their frequencies were significantly upregulated in MM patients when compared with healthy controls...
February 12, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29454372/a-novel-combination-of-bortezomib-lenalidomide-and-clarithromycin-produced-stringent-complete-response-in-refractory-multiple-myeloma-complicated-with-diabetes-mellitus-clinical-significance-and-possible-mechanisms-a-case-report
#5
Nobuo Takemori, Goro Imai, Kazuo Hoshino, Akishi Ooi, Masaru Kojima
BACKGROUND: In general, dexamethasone is a required component drug in various combination chemotherapies for treating multiple myeloma, and its efficacy has been widely recognized. However, administration of dexamethasone is known to cause various adverse effects including hyperglycemia which requires insulin therapy. During the course of treatment, we developed a novel effective dexamethasone-free combination regimen and evaluated it for its effect in multiple myeloma. CASE PRESENTATION: We report a case of 68-year-old Japanese woman with refractory advanced Bence-Jones-λ type multiple myeloma associated with diabetes mellitus...
February 18, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29452082/pre-treatment-red-blood-cell-distribution-width-provides-prognostic-information-in-multiple-myeloma
#6
Di Zhou, Peipei Xu, Miaoxin Peng, Xiaoyan Shao, Miao Wang, Jian Ouyang, Bing Chen
BACKGROUND: The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. METHODS: We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure...
February 13, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29450683/common-adverse-effects-of-novel-therapies-for-multiple-myeloma-mm-and-their-management-strategies
#7
REVIEW
Kristen B McCullough, Miriam A Hobbs, Jithma P Abeykoon, Prashant Kapoor
PURPOSE OF REVIEW: The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class...
February 15, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29450644/pi3k-akt-inhibitor-ly294002-potentiates-homoharringtonine-antimyeloma-activity-in-myeloma-cells-adhered-to-stromal-cells-and-in-scid-mouse-xenograft
#8
Ping Chen, Xiaofang Wen, Bin Wang, Diyu Hou, Hong Zou, Qin Yuan, Hui Yang, Jieqiong Xie, Huifang Huang
Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche...
February 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29450620/targeting-the-neddylation-pathway-in-cells-as-a-potential-therapeutic-approach-for-diseases
#9
REVIEW
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
https://www.readbyqxmd.com/read/29450576/immunopet-imaging-of-cd38-in-murine-lymphoma-models-using-89-zr-labeled-daratumumab
#10
Lei Kang, Dawei Jiang, Christopher G England, Todd E Barnhart, Bo Yu, Zachary T Rosenkrans, Rongfu Wang, Jonathan W Engle, Xiaojie Xu, Peng Huang, Weibo Cai
PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic...
February 15, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#11
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29445583/deep-sustained-response-to-daratumumab-monotherapy-associated-with-t-cell-expansion-in-triple-refractory-myeloma
#12
Saad Z Usmani, Imran Khan, Christopher Chiu, David Foureau, Lawrence J Druhan, Katherine Rigby, Tineke Casneuf, A Kate Sasser
Background: Daratumumab, a human CD38 monoclonal antibody that has direct on-tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as monotherapy or in combination with established regimens in patients with multiple myeloma with one or more prior lines of therapy. Case presentation: A male patient, who was 70 years of age at the time of diagnosis of multiple myeloma in 2011, relapsed after five lines of therapy, including autologous stem cell transplantation...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29445461/metastatic-prostate-cancer-with-bone-marrow-infiltration-mimicking-multiple-myeloma
#13
Pankaj Mathur, Daisy Alapat, Manoj Kumar, Sharmilan Thanendrarajan
Concomitant diagnosis of metastatic prostate cancer and a multiple myeloma in older male patients is challenging as both malignancies are usually associated with bone lesions. Exact knowledge, experience, and an interdisciplinary approach are required in order to differentiate between both malignancies and determine the exact treatment strategy.
February 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29444873/hypoxia-inducible-kdm3a-addiction-in-multiple-myeloma
#14
Sho Ikeda, Akihiro Kitadate, Fumito Abe, Naoto Takahashi, Hiroyuki Tagawa
In multiple myeloma (MM), the bone marrow (BM) microenvironment may contain a myeloma cell fraction that has acquired treatment resistance by undergoing an epigenetic gene expression change. Hypoxic stress is an important factor in the BM microenvironment. Recently, we demonstrated that miR-210 was upregulated in hypoxia and downregulated IRF4, which is known as an essential factor in myeloma oncogenesis in normoxia. In the study, we demonstrated that myeloma cells still showed a strong antiapoptotic phenotype despite IRF4 downregulation, suggesting that another antiapoptotic factor might be involved under hypoxic stress...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29441489/pirh2-mediates-the-sensitivity-of-myeloma-cells-to-bortezomib-via-canonical-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Li Yang, Jing Chen, Xiaoyan Han, Enfan Zhang, Xi Huang, Xing Guo, Qingxiao Chen, Wenjun Wu, Gaofeng Zheng, Donghua He, Yi Zhao, Yang Yang, Jingsong He, Zhen Cai
Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM...
February 13, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29440738/advantages-of-non-cryopreserved-autologous-hematopoietic-stem-cell-transplantation-against-a-cryopreserved-strategy
#16
M Sarmiento, P Ramírez, R Parody, M Q Salas, N Beffermann, V Jara, P Bertín, I Pizarro, C Lorca, E Rivera, M Galleguillos, M Ocqueteau, I Sánchez-Ortega, B Patiño, A Sureda
Autologous stem cell transplantation (auto-HSCT) is an effective treatment strategy for hematological malignancies. The standard mode of handling hematopoietic progenitors for the autologous procedure (CRYO) consists on its collection and freezing with dimethyl sulfoxide (DMSO) and its subsequent thawing and re-infusion. This process is toxic and expensive. Non-cryopreserved (non-CRYO) is a less expensive mode of auto-HSCT. We designed a comparative study between both strategies performed in two different centers to analyze the short-term complications...
February 13, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29440639/the-small-gtpase-rhou-lays-downstream-of-jak-stat-signaling-and-mediates-cell-migration-in-multiple-myeloma
#17
Sara Canovas Nunes, Martina Manzoni, Marco Pizzi, Elisa Mandato, Marilena Carrino, Laura Quotti Tubi, Renato Zambello, Fausto Adami, Andrea Visentin, Gregorio Barilà, Livio Trentin, Sabrina Manni, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29435979/ibrutinib-alone-or-with-dexamethasone-for-relapsed-or-relapsed-and-refractory-multiple-myeloma-phase-2-trial-results
#18
Paul G Richardson, William I Bensinger, Carol Ann Huff, Caitlin L Costello, Nikoletta Lendvai, Jesus G Berdeja, Larry D Anderson, David S Siegel, Daniel Lebovic, Sundar Jagannath, Jacob P Laubach, Keith E Stockerl-Goldstein, Long Kwei, Fong Clow, Laurence Elias, Zeena Salman, Thorsten Graef, Elizabeth Bilotti, Ravi Vij
Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design...
February 13, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29434978/activin-a-induces-apoptosis-of-mouse-myeloma-cells-via-the-mitochondrial-pathway
#19
Yuanyi Zhang, Yan Qi, Yang Zhao, Hongyan Sun, Jingyan Ge, Zhonghui Liu
Activin A is a pleiotropic cytokine belonging to the transforming growth factor β superfamily. Abnormal expression of activin A is associated with tumorigenesis. Multiple myeloma is characterized by the development of osteolytic disease, which ultimately leads to cachexia. However, the involvement of activin A in myeloma cell viability and apoptosis remains to be fully elucidated. For this purpose, mouse myeloma NS-1 cells were treated with activin A, and subsequently subjected to 5-bromo-2'-deoxyuridine analysis, Hoechst 33342 staining, flow cytometry and western blot analysis...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434974/dihydroartemisinin-treatment-of-multiple-myeloma-cells-causes-activation-of-c-jun-leading-to-cell-apoptosis
#20
Yong Wang, Xiaoyuan Xu, Xiaojian Wu, Weibin Chen, Fangmei Huang, Xiaomin Gui
The aim of the present study was to investigate the effect of dihydroartemisinin (DHA) on a multiple myeloma cell line. An MTT assay, flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) were used for the analysis of cell viability, cell cycle distribution and c-Jun N-terminal kinase (JNK) expression, respectively. Treatment of U266 cells using DHA caused a significant (P<0.05) decrease in cell viability compared with the control cells. An increase in the concentration of DHA from 1 to 100 µmol/l reduced cell viability from 87 to 35% compared with 100% in the control cultures at 48 h...
February 2018: Oncology Letters
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