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Rna myeloma

Yaping Zhong, Yonggang Zhang, Ping Wang, Hongxiu Gao, Chunling Xu, Hui Li
Multiple myeloma (MM) is a fatal hematological cancer characterized by clonal plasma cell proliferation in the bone marrow. MM has an increasing global incidence and a poor prognosis. There are limited treatment options available for MM, and this is further compounded by the development of drug resistance. The present study demonstrated that 7-{4-[Bis-(2-hydroxyethyl)-amino]-butoxy}-5-hydroxy-8-methoxy-2-phenylchromen-4-one (V8), a novel synthetic flavonoid, induced apoptosis in human MM RPMI 8226 cells in a dose- and time-dependent manner, using cell viability assays and flow cytometry...
October 2016: Oncology Letters
Siobhan V Glavey, Salomon Manier, Antonio Sacco, Karma Salem, Yawara Kawano, Juliette Bouyssou, Irene M Ghobrial, Aldo M Roccaro
Multiple myeloma is characterized by clonal proliferation of plasma cells within the bone marrow resulting in anemia, lytic bone lesions, hypercalcemia, and renal impairment. Despite advanced in our understanding of this complex disease in recent years, it is still considered an incurable malignancy. This is, in part, due to the highly heterogenous genomic and phenotypic nature of the disease, which is to date incompletely understood. It is clear that a deeper level of knowledge of the biological events underlying the development of these diseases is needed to identify new targets and generate effective novel therapies...
2016: Cancer Treatment and Research
Salomon Manier, Karma Salem, Siobhan V Glavey, Aldo M Roccaro, Irene M Ghobrial
Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes...
2016: Cancer Treatment and Research
Bruno Paiva, Juana Merino, Jesús F San Miguel
PURPOSE OF REVIEW: Although the input of multiparameter flow cytometry (MFC) into the clinical management of multiple myeloma patients has faced some reluctance, continuously growing evidence supports the utility of MFC in this disease. RECENT FINDINGS: MFC immunophenotyping of bone marrow and peripheral blood plasma cells affords cost-effective assessment of clonality, and provides prognostic information on the risk of progression in smoldering multiple myeloma, and the identification of active multiple myeloma patients with dismal outcome (e...
November 2016: Current Opinion in Oncology
Thea Kristin Våtsveen, Anne-Marit Sponaas, Erming Tian, Qing Zhang, Kristine Misund, Anders Sundan, Magne Børset, Anders Waage, Gaute Brede
BACKGROUND: Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. METHODS: Myeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this study...
August 31, 2016: Journal of Hematology & Oncology
Valentina Galimberti, Noa Kinor, Yaron Shav-Tal, Marco Biggiogera, Ansgar Brüning
Functional protein homeostasis is essential for the maintenance of normal cellular physiology, cell growth, and cell survival. Proteasome inhibition in cancer cells can disturb protein homeostasis in such a way that synthetic proteasome inhibitors like bortezomib may selectively kill myeloma cells. Solid cancer cells appear to respond less to bortezomib which may in part be due to a rescue mechanism of the unfolded protein response/endoplasmic reticulum stress mechanism which leads to a temporary shutdown of protein biosynthesis at the translational level...
October 2016: European Journal of Cell Biology
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...
August 11, 2016: Oncotarget
Maria Vaiou, Evanthia Pangou, Panagiotis Liakos, Nikos Sakellaridis, George Vassilopoulos, Konstantinos Dimas, Christos Papandreou
PURPOSE: Bortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells. METHODS: NCI-H929 and RPMI-8226 (human MM cell lines) were cultured with or without ET-1, BTZ, and inhibitors of the endothelin receptors. ET-1 levels were determined by ELISA, while the protein levels of its receptors and of the PI3K and MAPK pathways' components by western blot...
October 2016: Journal of Cancer Research and Clinical Oncology
Zhuanzhen Zheng, Zhenhua Qiao, Wenliang Chen, Rong Gong, Yalin Wang, Lianrong Xu, Yanping Ma, Li Zhang, Yujin Lu, Bo Jiang, Guoxia Li, Chunxia Dong
Multiple myeloma (MM) is one of the most common causes of mortality from hematological malignancy in China. Recent studies have demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) may exhibit a role in promoting the growth of cancer; however, the function of CIP2A in MM remains unknown. In the present study, the expression and molecular mechanism underlying the effects of CIP2A in patients with MM and in MM cell lines were elucidated. Firstly, the expression of CIP2A was detected in patients with MM and in MM cell lines by reverse transcription‑quantitative polymerase chain reaction...
September 2016: Molecular Medicine Reports
Mariko Ishibashi, Hideto Tamura, Mika Sunakawa, Asaka Kondo-Onodera, Namiko Okuyama, Yasuko Hamada, Keiichi Moriya, Inhak Choi, Koji Tamada, Koiti Inokuchi
B7 homolog 1 (B7-H1)-expressing myeloma cells not only inhibit myeloma-specific cytotoxic T lymphocytes (CTL), but also confer a proliferative advantage: resistance to antimyeloma chemotherapy. However, it remains unknown whether B7-H1 expressed on myeloma cells induces cellular responses associated with aggressive myeloma behaviors. To address this question, we analyzed the proliferation and drug sensitivity of B7-H1-expressing myeloma cells transfected with B7-H1-specific short-hairpin RNA or treated with programmed cell death (PD)-1-Fc-coupled beads...
September 2, 2016: Cancer Immunology Research
Bin-Bin Wang, Tao Wu
Multiple myeloma (MM) is a malignant tumor, characterized by dysplasia of clonal plasma cells in the bone marrow secreting large amounts of monoclonal immunoglobulin or fragments (M protein), resulting in damage in relevant organs or tissues. The biological complexity of MM is based on disrupted cancer pathways. Except the central role of cytogenetic abnormalities, epigenetic aberrations have also been shown to be involved in the occurrence and development of MM. Epigenetics of MM is mainly concentrated in the ways of DNA methylation, histone modifications and noncoding RNA, which have generated abnormal signaling pathways to regulate cell cycle and apoptosis of MM...
June 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jeong-Hyeon Ko, Seung Ho Baek, Dongwoo Nam, Won-Seok Chung, Seok-Geun Lee, Junhee Lee, Woong Mo Yang, Jae-Young Um, Kwang Seok Ahn
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently observed and closely linked with proliferation, survival, metastasis and angiogenesis of various cancer cells, and thus its inhibition can be considered a potential therapeutic strategy. We found that 3-formylchromone (3FC) inhibited both constitutive and inducible STAT3 activation in multiple myeloma (MM) cells. Besides the inhibition of STAT3 phosphorylation, 3FC also abrogated constitutive activity and nuclear translocation of STAT3...
October 2016: Immunopharmacology and Immunotoxicology
Arisa Haino, Tatsuya Ishikawa, Mineaki Seki, Masayuki Nashimoto
TRUE gene silencing (termed after tRNase Z(L)-utilizing efficacious gene silencing) is one of the RNA-directed gene silencing technologies, which utilizes an artificial small guide RNA (sgRNA) to guide tRNA 3' processing endoribonuclease, tRNase Z(L), to recognize a target RNA. sgRNAs can be taken up by cells without any transfection reagents and can downregulate their target RNA levels and/or induce apoptosis in human cancer cells. We have screened an sgRNA library containing 156 heptamer-type sgRNAs for the effect on viability of human myeloma and leukemia cells, and found that 20 of them can efficiently induce apoptosis in at least one of the cancer cell lines...
2016: Journal of Visualized Experiments: JoVE
Yanliang Chen, Chaoyue Zhang
Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic regulator of polyamines, ubiquitous molecules essential for cell proliferation and differentiation. Anti-SSAT antibodies (monoclonal antibodies [mAbs]) of high titer were prepared by immunizing BALB/c mice with multifocal intradermal injections and by fusing high-titer antibody-producing spleen cells with myeloma cells of SP2/0 origin. Four mAbs were selected for further characterization as classes and subclasses. Antibodies were produced by these three clones with high affinities ranging from 10(9) to 10(11) M(-1)...
June 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Yuxin Li, Xusheng Wang, Ji-Hoon Cho, Timothy I Shaw, Zhiping Wu, Bing Bai, Hong Wang, Suiping Zhou, Thomas G Beach, Gang Wu, Jinghui Zhang, Junmin Peng
Proteogenomics is an emerging approach to improve gene annotation and interpretation of proteomics data. Here we present JUMPg, an integrative proteogenomics pipeline including customized database construction, tag-based database search, peptide-spectrum match filtering, and data visualization. JUMPg creates multiple databases of DNA polymorphisms, mutations, splice junctions, partially trypticity, as well as protein fragments translated from the whole transcriptome in all six frames upon RNA-seq de novo assembly...
July 1, 2016: Journal of Proteome Research
Daeun Ryu, Hee Jin Kim, Je-Gun Joung, Hae-Ock Lee, Joon Seol Bae, Seok Jin Kim, Haesu Kim, Woong-Yang Park, Kihyun Kim
Immunoglobulin M multiple myeloma (IgM MM) is an extremely rare subtype of multiple myeloma with a poor clinical outcome. In this study, bone marrow aspirates of MM patients, including two cases of IgM MM, were analyzed by whole exome sequencing and RNA sequencing. Recurrent somatic mutations in the NRAS, KRAS, CCND1, DIS3, and TP53 genes were found in IgM MM and other types of MM, in agreement with previous studies. Overall transcription profiles of IgM and other types of MM clustered together, but separate from normal blood or peripheral plasma cells...
May 19, 2016: Oncotarget
G Ravi Kumar, Shikha Saxena, A P Sahoo, Uttara Chaturvedi, Satish Kumar, Lakshman Santra, G S Desai, Lakshyaveer Singh, Ashok K Tiwari
Newcastle Disease (ND) is one of the major causes of economic loss in the poultry industry. Newcastle Disease Virus (NDV) is a single-stranded, negative-sense enveloped RNA virus (Fam. Paramyxoviridae; Order Mononegavirales). In the present study three monoclonal antibodies (MAbs) were produced by polyethyleneglycol (PEG)-mediated fusion of lymphocytes sensitized to NDV Bareilly strain and myeloma cells. NDV possesses ability to agglutinate erythrocytes of avian species. All the three MAbs designated as 2H7, 3E9 and 3G6 caused hemagglutination inhibition of NDV by specifically binding to NDV...
March 2016: Indian Journal of Experimental Biology
Xi Yang, Yaping Zhang, Hong Liu, Zenghua Lin
Multiple myeloma is the second most prevalent type of blood cancer, representing approximately 1% of all cancers and 2% of all cancer deaths. There is therefore a strong need to identify critical targets in multiple myeloma neoplasia and progression. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein that regulates cancer cell viability and anchorage-independent growth and induces apoptosis. The present study investigated CIP2A function in the human multiple myeloma cell lines RPMI-8226 and NCI-H929 to determine whether it can serve as a potential therapeutic target...
2016: BioMed Research International
Li Zhang, Ling Pan, Bing Xiang, Huanling Zhu, Yu Wu, Meng Chen, Pujun Guan, Xingli Zou, C Alexander Valencia, Biao Dong, Jianjun Li, Liping Xie, Hongbing Ma, Fangfang Wang, Tian Dong, Xiao Shuai, Ting Niu, Ting Liu
Multiple myeloma (MM) is the second most common hematologic neoplasms and an appropriate in vivo environment for myeloma cells has potential implications for initiation, progression, and metastasis of MM. Exosomes, entities carrying microRNAs (miRNAs) to target locations, participate in the cross-talk between myeloma cells and nonmalignant components of the in vivo environment. This study disclosed the emerging roles of circulating exosome-associated miRNAs in drug resistance (DR) of MM. To this end, the medical records of consecutively hospitalized MM patients, who received novel agents-based therapies, were analyzed...
May 24, 2016: Oncotarget
D S Das, A Ray, A Das, Yan Song, B Oronsky, P Richardson, J Scicinski, D Chauhan, K C Anderson
The hypoxic bone-marrow (BM) microenvironment confers growth/survival and drug-resistance in multiple myeloma (MM) cells. Novel therapies targeting the MM cell in its hypoxic-BM milieu may overcome drug resistance. Recent studies led to the development of a novel molecule RRx-001 with hypoxia-selective epigenetic and Nitric Oxide-donating properties. Here we demonstrate that RRx-001 decreases the viability of MM cell lines and primary patient cells, as well as overcomes drug-resistance. RRx-001 inhibits MM cell growth in the presence of BM stromal cells...
April 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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