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Rna myeloma

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https://www.readbyqxmd.com/read/29296919/hypoxia-promotes-il-32-expression-in-myeloma-cells-and-high-expression-is-associated-with-poor-survival-and-bone-loss
#1
Muhammad Zahoor, Marita Westhrin, Kristin Roseth Aass, Siv Helen Moen, Kristine Misund, Katarzyna Maria Psonka-Antonczyk, Mariaserena Giliberto, Glenn Buene, Anders Sundan, Anders Waage, Anne-Marit Sponaas, Therese Standal
Multiple myeloma (MM) is a hematologic cancer characterized by expansion of malignant plasma cells in the bone marrow. Most patients develop an osteolytic bone disease, largely caused by increased osteoclastogenesis. The myeloma bone marrow is hypoxic, and hypoxia may contribute to MM disease progression, including bone loss. Here we identified interleukin-32 (IL-32) as a novel inflammatory cytokine expressed by a subset of primary MM cells and MM cell lines. We found that high IL-32 gene expression in plasma cells correlated with inferior survival in MM and that IL-32 gene expression was higher in patients with bone disease compared with those without...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296798/a-phase-2-study-of-panobinostat-with-lenalidomide-and-weekly-dexamethasone-in-myeloma
#2
Ajai Chari, Hearn J Cho, Amishi Dhadwal, Gillian Morgan, Lisa La, Katarzyna Zarychta, Donna Catamero, Erika Florendo, Nadege Stevens, Daniel Verina, Elaine Chan, Violetta Leshchenko, Alessandro Laganà, Deepak Perumal, Anna Huo-Chang Mei, Kaity Tung, Jami Fukui, Sundar Jagannath, Samir Parekh
Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290968/inhibition-of-ezh2-triggers-the-tumor-suppressive-mir-29b-network-in-multiple-myeloma
#3
Maria Angelica Stamato, Giada Juli, Enrica Romeo, Domenica Ronchetti, Mariamena Arbitrio, Daniele Caracciolo, Antonino Neri, Pierosandro Tagliaferri, Pierfrancesco Tassone, Nicola Amodio
Downregulation of tumor suppressor (TS) microRNAs (miRNAs) commonly occurs in human cancer, including multiple myeloma (MM). We previously demonstrated that miR-29b is a relevant TS miRNA, whose expression in MM cells is inhibited by HDAC4-dependent deacetylation. Here, we provide novel insights into epigenetic mechanisms suppressing miR-29b in MM. In MM patient-derived plasma cells, we found inverse correlation between miR-29b and EZH2 mRNA expression. Both siRNAs and pharmacologic inhibitors of EZH2 led to miR-29b upregulation, and this effect was ascribed to reduced H3K27-trimethylation (H3K27me3) of miR-29a/b-1 promoter regions...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273733/knockdown-of-long-non-coding-rna-h19-inhibits-multiple-myeloma-cell-growth-via-nf-%C3%AE%C2%BAb-pathway
#4
Yuanyuan Sun, Jing Pan, Ning Zhang, Wei Wei, Shanshan Yu, Limei Ai
Long non-coding RNAs (lncRNAs) are implicated in the complex network of cancer including Multiple myeloma (MM) and play important roles in tumor development. lncH19 was significantly up-regulated in multiple cancer types, suggesting it is a potential oncogene. However, the exact functions and downstream mechanisms are largely unknown. This study aimed to investigate whether H19 participates in the cell growth of MM and elucidate the underlying mechanism. We found that H19 was abnormally overexpressed in MM cell lines and sorted CD138+ MM bone marrow tissues...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228867/long-non-coding-rna-ccat1-promotes-multiple-myeloma-progression-by-acting-as-a-molecular-sponge-of-mir-181a-5p-to-modulate-hoxa1-expression
#5
Li Chen, Ning Hu, Chao Wang, Hongmian Zhao, Yueli Gu
Multiple myeloma (MM) is the second most common hematological cancer all over the world. Long non-coding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, little is known about its functional role and molecular mechanism in MM. The aim of this study was to investigate the clinical and biological significance of CCAT1 in MM. Our data showed that the relative expression levels of CCAT1 were significantly upregulated in MM tissues and cell lines compared with healthy donors and normal plasma cells (nPCs)...
December 11, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29212572/aberrant-lncrna-expression-in-multiple-myeloma
#6
Hui Meng, Lei Han, Chun Hong, Jinya Ding, Qianchuan Huang
Multiple myeloma (MM), a type of malignant tumor, is characterized by dysplasia of clonal plasma cells in the bone marrow. People with multiple myeloma will have damaged organs or tissues due to secreting of large amounts of monoclonal immunoglobulin or fragments (M protein). In spite of improved survivability by novel treatment strategies over the last decade, MM is still incurable by current therapy. Long non-conding RNA (lncRNA), with length of more than 200 nucleotides, has been reported to act as important regulators in many diseases, including multiple myeloma...
December 4, 2017: Oncology Research
https://www.readbyqxmd.com/read/29211023/charomers-interleukin-6-receptor-specific-aptamers-for-cellular-internalization-and-targeted-drug-delivery
#7
REVIEW
Ulrich Hahn
Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29205703/lncrna-neat1-promotes-dexamethasone-resistance-in-multiple-myeloma-by-targeting-mir-193a-mcl1-pathway
#8
Yilan Wu, Han Wang
Although dexamethasone (DEX) remains a first-line agent for multiple myeloma (MM) therapy, the development of DEX resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to DEX. This study demonstrated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX-resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to poor prognosis. The in-depth study revealed that during the development of DEX resistance in these cells, the miR-193a levels were decreased, which resulted in the increased expression of the target gene myeloid cell leukemia-1 (MCL1)...
December 4, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29203771/alu-dependent-rna-editing-of-gli1-promotes-malignant-regeneration-in-multiple-myeloma
#9
Elisa Lazzari, Phoebe K Mondala, Nathaniel Delos Santos, Amber C Miller, Gabriel Pineda, Qingfei Jiang, Heather Leu, Shawn A Ali, Anusha-Preethi Ganesan, Christina N Wu, Caitlin Costello, Mark Minden, Raffaella Chiaramonte, A Keith Stewart, Leslie A Crews, Catriona H M Jamieson
Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification of chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in 30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine RNA editing has recently emerged as a driver of cancer progression, genomic amplification combined with inflammatory cytokine activation of ADAR1 could stimulate MM progression and therapeutic resistance. Here, we report that high ADAR1 RNA expression correlates with reduced patient survival rates in the MMRF CoMMpass data set...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29203764/3d-genome-of-multiple-myeloma-reveals-spatial-genome-disorganization-associated-with-copy-number-variations
#10
Pengze Wu, Tingting Li, Ruifeng Li, Lumeng Jia, Ping Zhu, Yifang Liu, Qing Chen, Daiwei Tang, Yuezhou Yu, Cheng Li
The Hi-C method is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple myeloma (MM) and how it associates with genomic variation and gene expression. Our results show that Hi-C interaction matrices are biased by copy number variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS data can improve the detection of translocations...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29196615/expressed-fusion-gene-landscape-and-its-impact-in-multiple-myeloma
#11
A Cleynen, R Szalat, M Kemal Samur, S Robiou du Pont, L Buisson, E Boyle, M L Chretien, K Anderson, S Minvielle, P Moreau, M Attal, G Parmigiani, J Corre, N Munshi, H Avet-Loiseau
Multiple myeloma is a plasma cell malignancy characterized by recurrent IgH translocations and well described genomic heterogeneity. Although transcriptome profiles in multiple myeloma has been described, landscape of expressed fusion genes and their clinical impact remains unknown. To provide a comprehensive and detailed fusion gene cartography and suggest new mechanisms of tumorigenesis in multiple myeloma, we performed RNA sequencing in a cohort of 255 newly diagnosed and homogeneously treated multiple myeloma patients with long follow-up...
December 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29166413/comprehensive-molecular-profiling-of-718-multiple-myelomas-reveals-significant-differences-in-mutation-frequencies-between-african-and-european-descent-cases
#12
Zarko Manojlovic, Austin Christofferson, Winnie S Liang, Jessica Aldrich, Megan Washington, Shukmei Wong, Daniel Rohrer, Scott Jewell, Rick A Kittles, Mary Derome, Daniel Auclair, David Wesley Craig, Jonathan Keats, John D Carpten
Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#13
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29095438/baff-is-involved-in-macrophage-induced-bortezomib-resistance-in-myeloma
#14
Jing Chen, Donghua He, Qingxiao Chen, Xing Guo, Li Yang, Xuanru Lin, Yi Li, Wenjun Wu, Yang Yang, Jingsong He, Enfan Zhang, Qing Yi, Zhen Cai
We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29089084/-knockdown-of-nuclear-protein-1-nupr1-gene-inhibits-proliferation-and-promotes-apoptosis-of-human-multiple-myeloma-u266-cells
#15
Chensi Zeng, Bei Yi, Xingxin Li, Jianbin Chen
Objective To construct nuclear protein 1-short hairpin RNA (NUPR1-shRNA)-expressing lentiviral vector targeting NUPR1 gene, and investigate the effect of NUPR1 gene silencing on the proliferation and apoptosis of human multiple myeloma U266 cells. Methods The normal plasma cells were used as controls and the mRNA expression level of NUPR1 in myeloma cell lines U266 and RPMI8226 were detected by quantitative real-time PCR (qRT-PCR). Then the shRNA plasmid targeting NUPR1 gene was constructed and transfected into U266 cells...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29073933/role-of-tumor-suppressor-p53-and-micro-rna-interplay-in-multiple-myeloma-pathogenesis
#16
REVIEW
Jahangir Abdi, Nasrin Rastgoo, Lihong Li, Wenming Chen, Hong Chang
The molecular mechanisms underlying dysregulated wild type (wt) p53 in multiple myeloma (MM) have been subjects of intense investigation for years. Indeed, correlation of rarely occurring TP53 gene mutations or deletions with adverse clinical outcomes in MM patients is strongly established, while in majority of cases wtp53 seems to be non-functional or dysregulated bearing a high clinical impact. Interestingly, findings from recent investigations show that micro-RNAs (miRNAs) may contribute to suppression of wtp53 in MM, as they are now known to function as key regulatory elements in the p53 network...
October 26, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28966938/rna-processing-a-new-player-of-genomic-instability-in-multiple-myeloma
#17
EDITORIAL
Matteo Marchesini, Elena Fiorini, Simona Colla
No abstract text is available yet for this article.
July 2017: Oncoscience
https://www.readbyqxmd.com/read/28944848/cmip-is-oncogenic-in-human-gastric-cancer-cells
#18
Jianlin Zhang, Jin Huang, Xingyu Wang, Weidong Chen, Qinqing Tang, Maoyong Fang, Yeben Qian
Gastric cancer is one of the most common cancers and the second leading cause of cancer‑associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c‑Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T‑cell lymphoma...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28938651/positive-transcription-elongation-factor-b-p-tefb-is-a-therapeutic-target-in-human-multiple-myeloma
#19
Yu Zhang, Liang Zhou, Yun Leng, Yun Dai, Robert Z Orlowski, Steven Grant
The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138(+) MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903565/liquid-biopsies-the-clinics-and-the-molecules
#20
V Kubaczková, L Sedlarikova, B Bollová, V Sandecká, M Stork, L Pour, S Sevcikova
Unlike bone marrow biopsies, liquid biopsies represent a gentler, more accessible, less painful, repeatable and more comprehensive approach to get biologically relevant information about the entire tumor but also about treatment response and level of minimal residual disease. This is all possible since peripheral blood contains not only circulating tumor cells but also many circulating molecules of nucleic acids (microRNA, cell-free DNA, long non-coding RNA etc.). Multiple myeloma is a genetically heterogeneous disease characterized by multifocal tumor deposits in the bone marrow but also focal lesions elsewhere...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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