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Multiple myeloma

Caterina Musolino, Giacomo Oteri, Alessandro Allegra, Manuela Mania, Angela D'Ascola, Angela Avenoso, Vanessa Innao, Andrea Gaetano Allegra, Salvatore Campo
Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ...
March 15, 2018: Annals of Hematology
Irena Misiewicz-Krzeminska, Luis Antonio Corchete, Elizabeta A Rojas, Joaquín Martínez-López, Ramón García-Sanz, Albert Oriol, Joan Bladé, Juan José Lahuerta, Jesús San Miguel, María Victoria Mateos, Norma C Gutiérrez
Protein analysis in bone marrow samples from patients with multiple myeloma has been limited by the low protein concentration obtained after CD138+ selection. A novel approach based on capillary nano-immunoassay could make it possible to automatically quantify dozens of proteins from each myeloma sample. Here, we present a method for the accurate and robust quantification of the expression of multiple proteins extracted from CD138-purified multiple myeloma samples frozen in RLT Plus buffer, which is commonly used for nucleic acid preservation and isolation...
March 15, 2018: Haematologica
Berdien E Oortgiesen, Roshna Azad, Marc H Hemmelder, Robby E Kibbelaar, Nic J G M Veeger, Joost C de Vries, Eric N van Roon, Mels Hoogendoorn
No abstract text is available yet for this article.
March 15, 2018: Haematologica
Laurens E Franssen, Inger S Nijhof, Suzana Couto, Mark-David Levin, Gerard M J Bos, Annemiek Broijl, Saskia K Klein, Yan Ren, Maria Wang, Harry R Koene, Andries C Bloem, Aart Beeker, Laura M Faber, Ellen van der Spek, Reinier Raymakers, Roos J Leguit, Pieter Sonneveld, Sonja Zweegman, Henk Lokhorst, Tuna Mutis, Anjan Thakurta, Xiaozhong Qian, Niels W C J van de Donk
No abstract text is available yet for this article.
March 15, 2018: Haematologica
Kinga A Kocemba-Pilarczyk, Barbara Ostrowska, Sonia Trojan, Ecce Aslan, Dorota Kusior, Małgorzata Lasota, Claire Lenouvel, Joanna Dulińska-Litewka
Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-Allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions...
March 15, 2018: Acta Biochimica Polonica
Jin Ah Cha, Hyo-Sook Song, Beomku Kang, Moon Nyeo Park, Kyoung Sun Park, Sung-Hoon Kim, Bum-Sang Shim, Bonglee Kim
Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP)...
March 15, 2018: International Journal of Molecular Sciences
Lucía Fernández, Alejandra Leivas, Jaime Valentín, Adela Escudero, Dolores Corral, Raquel de Paz, Maria Vela, David Bueno, Rebeca Rodríguez, Juan Manuel Torres, Mariana Díaz-Almirón, Eduardo López-Collazo, Joaquin Martinez-Lopez, Antonio Pérez-Martínez
BACKGROUND: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use. STUDY DESIGN AND METHODS: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line...
March 14, 2018: Transfusion
Zhaoyun Liu, Hui Liu, Xin Yuan, Yihao Wang, Lijuan Li, Guojin Wang, Jia Song, Zonghong Shao, Rong Fu
Pim-2 is a serine/threonine protein kinase that is highly expressed in various types of cancer, with essential roles in the regulation of signal transduction cascades, which promote cell survival and proliferation. The present study demonstrated that Pim-2 was expressed in cells lines derived from hematopoietic tumors and lung cancer. In vitro , downregulation of Pim-2 by short interfering RNA inhibited proliferation and delayed G0 /G1 cell cycle progression in K562 leukemia, RPMI-8226 multiple myeloma, and H1299 and A549 non-small cell lung carcinoma cell lines...
April 2018: Oncology Letters
Qingqing Pan, Yaping Luo, Xinxin Cao, Yanru Ma, Fang Li
A 60-year-old woman diagnosed with multiple myeloma was referred for Ga-pentixafor PET/CT for evaluation of the disease. Diffuse and intense radioactivity throughout the axial and proximal appendicular skeleton was noted on PET/CT images, suggestive of extensive involvement of multiple myeloma.
March 13, 2018: Clinical Nuclear Medicine
Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiro Fujii, Kiyoe Kurahashi, Sumiko Yoshida, Kumiko Kagawa, Itsuro Endo, Kenichi Aihara, Mariko Ikuo, Kohji Itoh, Koichiro Hayashi, Michihiro Nakamura, Masahiro Abe
Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death...
February 13, 2018: Oncotarget
Song Xu, Kim De Veirman, Ann De Becker, Karin Vanderkerken, Ivan Van Riet
Multiple myeloma (MM) is a malignant plasma cell (PC) disorder, characterized by a complex interactive network of tumour cells and the bone marrow (BM) stromal microenvironment, contributing to MM cell survival, proliferation and chemoresistance. Mesenchymal stem cells (MSCs) represent the predominant stem cell population of the bone marrow stroma, capable of differentiating into multiple cell lineages, including fibroblasts, adipocytes, chondrocytes and osteoblasts. MSCs can migrate towards primary tumours and metastatic sites, implying that these cells might modulate tumour growth and metastasis...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
Tomofumi Yamamoto, Nobuyoshi Kosaka, Yutaka Hattori, Takahiro Ochiya
Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs) were shown to modulate the expression of genes critical for MM pathogenesis...
March 12, 2018: Journal of Clinical Medicine
Jane Cho, Nicole Siegel, Manju L Subramanian, Howard Ying, Steven Ness
PURPOSE: To describe a case of neovascular glaucoma from cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-negative patient with immunosuppression after stem-cell transplant for multiple myeloma. METHODS: Retrospective case report. RESULTS: A 71-year-old man on monthly infusion of daratumumab for multiple myeloma after stem-cell transplant presenting with a 2-week history of floaters, photophobia, and blurry vision was found to have polymerase chain reaction-confirmed CMV retinitis associated with diffuse occlusive vasculitis...
March 12, 2018: Retinal Cases & Brief Reports
Yue Yang, Long Chen, Yuan Jia, Yang Liu, Lei Wen, Yaoxian Liang, Yuan An, Shi Chen, Yin Su, Zhanguo Li
To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed...
March 13, 2018: Clinical Rheumatology
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Lina Xu, Giles Tetteh, Jana Lipkova, Yu Zhao, Hongwei Li, Patrick Christ, Marie Piraud, Andreas Buck, Kuangyu Shi, Bjoern H Menze
The identification of bone lesions is crucial in the diagnostic assessment of multiple myeloma (MM).68 Ga-Pentixafor PET/CT can capture the abnormal molecular expression of CXCR-4 in addition to anatomical changes. However, whole-body detection of dozens of lesions on hybrid imaging is tedious and error prone. It is even more difficult to identify lesions with a large heterogeneity. This study employed deep learning methods to automatically combine characteristics of PET and CT for whole-body MM bone lesion detection in a 3D manner...
2018: Contrast Media & Molecular Imaging
Praful Ravi, Shaji K Kumar, James R Cerhan, Matthew J Maurer, David Dingli, Stephen M Ansell, S Vincent Rajkumar
Advances in therapy in recent years have led investigators to challenge the dogma that multiple myeloma (MM) is incurable. We assessed overall (OS) and progression-free survival (PFS) of young patients ( ≤ 50 years) with MM and compared outcomes with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Hodgkin lymphoma (HL). All patients ≤ 50 years with newly diagnosed MM (n = 212), FL (n = 168), DLBCL (n = 195), and HL (n = 233) between 1 January 2005 and 31 December 2015 were included...
February 28, 2018: Blood Cancer Journal
Ester Lozano, Tania Díaz, Mari-Pau Mena, Guillermo Suñe, Xavier Calvo, Marcos Calderón, Lorena Pérez-Amill, Vanina Rodríguez, Patricia Pérez-Galán, Gaël Roué, M Teresa Cibeira, Laura Rosiñol, Ignacio Isola, Luis-Gerardo Rodríguez-Lobato, Beatriz Martin-Antonio, Joan Bladé, Carlos Fernández de Larrea
Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j ( LILRB1 ), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9. Decreased CD85j expression could also be detected in the premalignant condition MGUS, suggesting that loss of CD85j may be an early event promoting tumor immune escape...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhong-Ling Wei, Cai-Ming Pan, Yi-Zhi Jiang, Yan-Dai, Lai-Quan Huanguang, Dong-Ping Huang
High-dose chemotherapy combined with autologous hematopoietic stem-cell transplantation (ASCT) is the first-line treatment for multiple myeloma. Yet, some patients will relapse. Testicular plasmacytoma which rarely happens can be isolated or associated with progressive multiple myeloma. Here, we report a case of multiple myeloma (MM) undergoing ASCT when the patient obtained complete remission. He developed painless right testicular swelling after nearly 3 years since the ASCT. After radical orchiectomy, histopathology showed diffuse abnormal plasma cells infiltration of the testicular tissue...
January 2018: Annals of Clinical and Laboratory Science
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