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Myeloma Multiple

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https://www.readbyqxmd.com/read/28933784/inhibition-of-the-deubiquitinase-usp5-leads-to-c-maf-protein-degradation-and-myeloma-cell-apoptosis
#1
Siyu Wang, Jiaxiang Juan, Zubin Zhang, Yanyun Du, Yujia Xu, Jiefei Tong, Biyin Cao, Michael F Moran, Yuanying Zeng, Xinliang Mao
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933361/lysosomal-storage-disorders-and-malignancy
#2
REVIEW
Gregory M Pastores, Derralynn A Hughes
Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933264/from-a-better-understanding-of-the-mechanisms-of-action-of-histone-deacetylases-inhibitors-to-the-progress-of-the-treatment-of-malignant-lymphomas-and-plasma-cell-myeloma
#3
Romeo-Gabriel Mihăilă
BACKGROUND: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. OBJECTIVE: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. METHOD: A minireview was achieved using the articles published in PubMed in the last two years and the new patents made in this field...
September 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#4
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932581/catch-me-if-you-can-how-to-make-the-best-use-of-pleural-effusion
#5
Lianjun Lin, Qian Han, Zhonghui Liu, Huiying Xu, Yanping Wu, Jixin Zhang, Xinmin Liu
Etiology diagnosis of pleural effusion is a commonly encountered yet challenging problem. How to make the best use of pleural effusion evokes thinking. Myelomatous pleural effusion (MPE) is a rare condition and has been reported sporadically. We report an extremely rare case of multiple myeloma (MM) [IgD-lambda (λ) type, stage III B] with MPE as initial presentation and complicated with massive pericardial effusions during the progression of the disease. Cytological identification of malignant plasma cells in pleural effusion is the most direct method to diagnose MPE...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28931820/the-non-canonical-poly-a-polymerase-fam46c-acts-as-an-onco-suppressor-in-multiple-myeloma
#6
Seweryn Mroczek, Justyna Chlebowska, Tomasz M Kuliński, Olga Gewartowska, Jakub Gruchota, Dominik Cysewski, Vladyslava Liudkovska, Ewa Borsuk, Dominika Nowis, Andrzej Dziembowski
FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28930776/a-phase1b-dose-escalation-study-of-recombinant-circularly-permuted-trail-in-patients-with-relapsed-or-refractory-multiple-myeloma
#7
Jian Hou, Lugui Qiu, Yaozhong Zhao, Xuejun Zhang, Yan Liu, Zhao Wang, Fang Zhou, Yun Leng, Shifang Yang, Hao Xi, Fuxu Wang, Bing Zhu, Wenming Chen, Peng Wei, Xiangjun Zheng
OBJECTIVES: Circularly permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT), or CPT, is a novel antitumor drug candidate. This phase 1b study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent CPT in patients with relapsed or refractory multiple myeloma (RRMM), and aimed to identify the recommended dose for the phase 2 study. MATERIALS AND METHODS: Patients received single or multiple doses (once daily for 5 consecutive days per 21-d cycle) of CPT intravenous infusion at doses of 5, 6...
September 19, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28928810/characteristics-of-baff-and-april-factor-expression-in-multiple-myeloma-and-clinical-significance
#8
Jing Pan, Yuanyuan Sun, Ning Zhang, Jianming Li, Fangxin Ta, Wei Wei, Shanshan Yu, Limei Ai
The characteristics of the proliferation of B-cell activating factor (BAFF) and the proliferation-inducing ligand (APRIL) mRNA expression in mononuclear cell in multiple myeloma patients were detected, and the correlation was analyzed between the BAFF and APRIL concentrations in plasma and tumor burden parameters of multiple myeloma. Bone marrow samples from 60 patients with multiple myeloma and 20 healthy persons taken as controls, were collected. Bone marrow mononuclear cells (BMMCs) were harvested, and plasma was extracted...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#9
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28927072/arsenic-trioxide-potentiates-sensitivity-of-multiple-myeloma-cells-to-lenalidomide-by-upregulating-cereblon-expression-levels
#10
Yuan Jian, Wen Gao, Chuanying Geng, Huixing Zhou, Yun Leng, Yanchen Li, Wenming Chen
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926977/mouse-monoclonal-antibodies-generated-from-full-length-human-cereblon-detection-of-cereblon-protein-in-patients-with-multiple-myeloma
#11
Xiubao Chang, Qinqin Xu, Yuexian Hou, Cynthia Li, Ye Xu, A Keith Stewart
Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs' action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor...
September 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28924071/-a-case-of-a-solitary-plasmacytoma-extending-into-the-extradural-space
#12
Hiroshi Nakano, Koichi Kato, Shunsuke Nomura, Masanori Nakagawa, Takashi Higa, Shigeru Kadoyama, Takakazu Kawamata, Hiroshi Ujiie, Akira Teramoto
Plasmacytomas are characterized by a monoclonal proliferation of plasma cells, and constitute the bulk of multiple myeloma. A solitary plasmacytoma is a rare entity, and is even more unlikely to occur intracranially. Here we present a 62-year-old man with an intracranial tumor. Magnetic resonance imaging revealed a large mass on the surface of the right fronto-parieto-temporal region, with extradurally directed growth. The tumor was enhanced homogenously by gadolinium, with dural tail-like findings, which resembled a meningioma...
September 2017: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/28923846/detection-of-circulating-plasma-cells-in-multiple-myeloma
#13
Catherine Alix-Panabières, Klaus Pantel
No abstract text is available yet for this article.
September 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28923647/is-cytomegalovirus-surveillance-necessary-for-patients-with-low-reactivation-risk-in-an-autologous-hematopoietic-cell-transplantation-setting
#14
A H Kaya, E Tekgunduz, S Akpinar, H Batgi, F Bekdemir, O Kayikci, S Namdaroglu, B U Ulu, M S Dal, M K Cakar, S Korkmaz, F Altuntas
BACKGROUND: In an autologous hematopoietic cell transplantation (AHCT) setting, routine cytomegalovirus (CMV) surveillance is not indicated except in high-risk situations. On the other hand, some studies reported increased CMV reactivation in AHCT setting as a result of incorporation of novel agents into treatment algorithms, such as bortezomib and rituximab. We retrospectively analyzed CMV reactivation and infection rates in patients with no high-risk features, who were treated with AHCT...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923389/1-4-naphthoquinones-as-inhibitors-of-itch-a-hect-domain-e3-ligase-and-tumor-growth-suppressors-in-multiple-myeloma
#15
Yi-Min Liu, Wei-Chun HuangFu, Han-Li Huang, Wei-Cheng Wu, Yi-Lin Chen, Yun Yen, Hsiang-Ling Huang, Chih-Ying Nien, Mei-Jung Lai, Shiow-Lin Pan, Jing-Ping Liou
A series of 1,4-naphthoquinones (10a-10q) were synthesized and evaluated for anticancer activity. Compound 10e was identified as an inhibitor of Itch, a HECT domain-E3 ligase. In an evaluation of in vivo efficacy, 10e exhibited remarkable anticancer activity with TGI values of 98.3% and 100% at 25 mg/kg and 50 mg/kg orally daily, respectively, against human RPMI-8226 multiple myeloma xenograft. Treatment with 10e also showed a decrease of Itch level in human RPMI-8226 multiple myeloma cells. Thus 10e is a lead compound for further development of inhibitors targeting E3 ligase for treatment of multiple myeloma...
September 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28922455/stem-cell-mobilization-in-patients-with-dialysis-dependent-multiple-myeloma-report-of-the-polish-multiple-myeloma-group
#16
Anna Waszczuk-Gajda, Joanna Drozd-Sokołowska, Piotr Boguradzki, Jarosław Dybko, Tomasz Wróbel, Grzegorz Władysław Basak, Krzysztof Mądry, Emilian Snarski, Grzegorz Charliński, Ewa Frączak, Joanna Matuszkiewicz-Rowińska, Marian Klinger, Hanna Augustyniak-Bartosik, Magdalena Krajewska, Paweł Żebrowski, Maria Król, Elżbieta Urbanowska, Artur Jurczyszyn, Michał Taszner, Wieslaw Wiktor Jędrzejczak, Jadwiga Dwilewicz-Trojaczek
INTRODUCTION: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. MATERIALS AND METHODS: Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Multiple Myeloma Group...
September 18, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28922292/advances-in-delivery-of-ambulatory-autologous-stem-cell-transplantation-for-multiple-myeloma
#17
Jack Khouri, Navneet S Majhail
PURPOSE OF REVIEW: Autologous stem cell transplantation (ASCT) is generally performed in the inpatient setting in its entirety. Several centers have demonstrated the feasibility of performing ASCT for myeloma in the ambulatory setting. We review the safety, cost-effectiveness, complications and outcomes of outpatient ASCT for myeloma. RECENT FINDINGS: Published studies are heterogeneous but suggest that outpatient ASCT for myeloma is cost-effective and associated with a shorter or no initial hospitalization, albeit there is a high rate of readmission for complications...
September 15, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28920949/autologous-hematopoietic-cell-transplantation-for-multiple-myeloma-patients-with-renal-insufficiency-a-center-for-international-blood-and-marrow-transplant-research-analysis
#18
A Mahindra, P Hari, R Fraser, M Fei, J Huang, J Berdeja, N Callander, L Costa, M A Diaz, C Freytes, R P Gale, S Girnius, L Holmberg, M Kharfan-Dabaja, S Kumar, R Kyle, H Lazarus, C Lee, A Maiolino, J Moreb, T Nishihori, A Pawarode, A Saad, B N Savani, J Schriber, B William, B M Wirk, A Krishnan, Y Nieto, A D'Souza
Autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients with renal insufficiency (RI) is controversial. Patients who underwent AHCT for MM between 2008 and 2013 were identified (N=1492) and grouped as normal/mild (⩾60 mL/min), N=1240, moderate (30-59), N=185 and severe RI (<30), N=67 based on Modification of Diet in Renal Disease. Multivariate analyses of non-relapse mortality (NRM), relapse, PFS and overall survival (OS) were performed. Of the 67 patients with severe RI, 35 were on dialysis prior to AHCT...
September 18, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28920142/acupuncture-for-reduction-of-symptom-burden-in-multiple-myeloma-patients-undergoing-autologous-hematopoietic-stem-cell-transplantation-a-randomized-sham-controlled-trial
#19
Gary Deng, Sergio Giralt, David J Chung, Heather Landau, Jonathan Siman, Benjamin Search, Marci Coleton, Emily Vertosick, Nathan Shapiro, Christine Chien, Xin S Wang, Barrie Cassileth, Jun J Mao
PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy...
September 17, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28918747/omega-3-polyunsaturated-fatty-acids-eicosapentaenoic-acid-and-docosahexaenoic-acid-enhance-dexamethasone-sensitivity-in-multiple-myeloma-cells-by-the-p53-mir-34a-bcl-2-axis
#20
Xianping Dai, Mengshun Li, Feng Geng
Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. q-PCR analysis revealed that miR-34a could be significantly induced by PUFAs in U266 and primary MM cells. Transfection with miR-34a antagonist or miR-34a agomir could restore or suppress the dexamethasone sensitivity in U266 cells...
July 2017: Biochemistry. Biokhimii︠a︡
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