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https://www.readbyqxmd.com/read/27895482/nanoparticle-based-strategy-for-personalized-b-cell-lymphoma-therapy
#1
Nicola M Martucci, Nunzia Migliaccio, Immacolata Ruggiero, Francesco Albano, Gaetano Calì, Simona Romano, Monica Terracciano, Ilaria Rea, Paolo Arcari, Annalisa Lamberti
B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27892767/epigenetic-modifications-in-multiple-myeloma-recent-advances-on-the-role-of-dna-and-histone-methylation
#2
Nicola Amodio, Patrizia D'Aquila, Giuseppe Passarino, Pierfrancesco Tassone, Dina Bellizzi
Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway...
November 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27807282/genetic-interrogation-of-circulating-multiple-myeloma-cells-at-single-cell-resolution
#3
Jens G Lohr, Sora Kim, Joshua Gould, Birgit Knoechel, Yotam Drier, Matthew J Cotton, Daniel Gray, Nicole Birrer, Bang Wong, Gavin Ha, Cheng-Zhong Zhang, Guangwu Guo, Matthew Meyerson, Andrew J Yee, Jesse S Boehm, Noopur Raje, Todd R Golub
Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulate MM in the bone marrow...
November 2, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27782060/identification%C3%A2-of%C3%A2-long%C3%A2-non-coding%C3%A2-rnas-deregulated%C3%A2-in%C3%A2-multiple%C3%A2-myeloma%C3%A2-cells%C3%A2-resistant%C3%A2-to-proteasome%C3%A2-inhibitors
#4
Ehsan Malek, Byung-Gyu Kim, James J Driscoll
While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance...
October 6, 2016: Genes
https://www.readbyqxmd.com/read/27779672/knockdown-of-macrophage-inhibitory-cytokine-1-in-rpmi-8226-human-multiple-myeloma-cells-inhibits-osteoclastic-differentiation-through-inhibiting-the-rankl-erk1-2-signaling-pathway
#5
Mingzhou Yuan, Junmin Chen, Zhiyong Zeng
Patients with multiple myeloma (MM) often develop myeloma bone disease (MBD). The development of MBD from MM is considered to be caused by an abnormal bone marrow microenvironment. Macrophage inhibitory cytokine-1 (MIC-1) is a member of the transforming growth factor‑β superfamily. In patients with MM, MIC‑1 is expressed at high levels, however, whether this increased expression of MIC‑1 is associated with the development of MBD from MM remains to be elucidated. The present study investigated whether MIC‑1 is essential for the osteoclastic differentiation of peripheral blood mononuclear cells (PBMNCs) by using a co‑culture system, in which the PBMNCs were co‑cultured with RPMI‑8226 cells...
October 24, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27773931/the-lin28b-let-7-axis-is-a-novel-therapeutic-pathway-in-multiple-myeloma
#6
S Manier, J T Powers, A Sacco, S V Glavey, D Huynh, M R Reagan, K Z Salem, M Moschetta, J Shi, Y Mishima, C Roche-Lestienne, X Leleu, A M Roccaro, G Q Daley, I M Ghobrial
MYC is a major oncogenic driver of multiple myeloma (MM) and yet almost no therapeutic agents exist that target MYC in MM. Here we report that the let-7 biogenesis inhibitor LIN28B correlates with MYC expression in MM and is associated with adverse outcome. We also demonstrate that the LIN28B/let-7 axis modulates the expression of MYC, itself a let-7 target. Further, perturbation of the axis regulates the proliferation of MM cells in vivo in a xenograft tumor model. RNA-sequencing and gene set enrichment analyses of CRISPR-engineered cells further suggest that the LIN28/let-7 axis regulates MYC and cell cycle pathways in MM...
November 11, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27773219/short-hairpin-rna-silencing-of-interleukin-6-in-human-bone-marrow-derived-mesenchymal-stromal-cells-inhibits-multiple-myeloma-cell-growth
#7
Hoon Koon Teoh, Pei Pei Chong, Maha Abdullah, Zamberi Sekawi, Geok Chin Tan, Chooi Fun Leong, Soon Keng Cheong
No abstract text is available yet for this article.
February 2016: Pathology
https://www.readbyqxmd.com/read/27754828/small-interfering-rna-mediated-silencing-of-nicotinamide-phosphoribosyltransferase-nampt-and-lysosomal-trafficking-regulator-lyst-induce-growth-inhibition-and-apoptosis-in-human-multiple-myeloma-cells-a-preliminary-study
#8
Ivyna Pau Ni Bong, Ching Ching Ng, Shaik Kamal Fakiruddin, Moon Nian Lim, Zubaidah Zakaria
Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers...
November 10, 2016: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27703527/v8-induces-apoptosis-and-the-endoplasmic-reticulum-stress-response-in-human-multiple-myeloma-rpmi-8226-cells-via-the-perk-eif2%C3%AE-atf4-signaling-pathway
#9
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
https://www.readbyqxmd.com/read/27696257/epigenetics-in-multiple-myeloma
#10
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
https://www.readbyqxmd.com/read/27696256/genomic-aberrations-in-multiple-myeloma
#11
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
https://www.readbyqxmd.com/read/27606694/utility-of-flow-cytometry-studies-in-the-management-of-patients-with-multiple-myeloma
#12
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
https://www.readbyqxmd.com/read/27581518/erythropoietin-epo-receptor-signaling-induces-cell-death-of-primary-myeloma-cells-in-vitro
#13
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
https://www.readbyqxmd.com/read/27567537/the-stress-inducible-transcription-factor-atf4-accumulates-at-specific-rrna-processing-nucleolar-regions-after-proteasome-inhibition
#14
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
https://www.readbyqxmd.com/read/27533084/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#15
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
https://www.readbyqxmd.com/read/27530445/endothelin-1-et-1-induces-resistance-to-bortezomib-in-human-multiple-myeloma-cells-via-a-pathway-involving-the-etb-receptor-and-upregulation-of-proteasomal-activity
#16
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
https://www.readbyqxmd.com/read/27484817/cip2a-regulates-proliferation-and-apoptosis-of-multiple-myeloma-cells
#17
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
https://www.readbyqxmd.com/read/27440711/myeloma-drug-resistance-induced-by-binding-of-myeloma-b7-h1-pd-l1-to-pd-1
#18
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
https://www.readbyqxmd.com/read/27342538/-role-of-biology-based-on-epigenetics-in-multiple-myeloma
#19
REVIEW
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
https://www.readbyqxmd.com/read/27324722/3-formylchromone-inhibits-proliferation-and-induces-apoptosis-of-multiple-myeloma-cells-by-abrogating-stat3-signaling-through-the-induction-of-pias3
#20
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
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