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Molecular myeloma

Chia-Hung Yen, Hui-Hua Hsiao
Multiple myeloma with clonal plasma expansion in bone marrow is the second most common hematologic malignancy in the world. Though the improvement of outcomes from the achievement of novel agents in recent decades, the disease progresses and leads to death eventually due to the elusive nature of myeloma cells and resistance mechanisms to therapeutic agents. In addition to the molecular and genetic basis of resistance pathomechanisms, the bone marrow microenvironment also contributes to disease progression and confers drug resistance in myeloma cells...
November 7, 2018: International Journal of Molecular Sciences
H-B Rui, X-Q Zheng, M-Y Lin, A-P Yang
OBJECTIVE: Myeloma poses a serious risk for people's health and life quality. Molecular targeted treatment of myeloma emerges as a promising therapy. This study aimed to determine the effect of Sirtuin 6 on myeloma KM-HM_(31) cell aging and provide evidence for clinical treatment. MATERIALS AND METHODS: Myeloma KM-HM_(31) cell aging model induced by Carbamide peroxide (CP) was generated. Cells were transfected with Sirtuin 6 over-expression plasmid and specific siRNA...
October 2018: European Review for Medical and Pharmacological Sciences
T Liu, H-W Fan, S Lu, S-Q Wang, F Li
OBJECTIVE: Myeloma seriously threats human life and health and needs more efficacy treatment method in the clinic. MiR-126 regulates cell proliferation and apoptosis. This study explores the regulatory role of miR-126 in myeloma and related molecular mechanism. MATERIALS AND METHODS: MiR-126 and control were synthesized and transfected to myeloma cell line Karpas707 using Lipofectamine. Cell apoptosis was evaluated by MTT assay, caspase-3 activity detection, and flow cytometry...
October 2018: European Review for Medical and Pharmacological Sciences
Zheng C He, Xin Y Li, Yong L Guo, Dan Ma, Qin Fang, Ling L Ren, Zhao Y Zhang, Weili Wang, Zheng Y Yu, Peng Zhao, Ji S Wang
Osteoclasts (OCs) play an essential role in bone destruction in patients with multiple myeloma (MM). Bortezomib can ameliorate bone destruction in patients with MM, but advanced MM often resists bortezomib. We studied the molecular mechanisms of bortezomib tolerance in MM. The expression of the MM-related genes in newly diagnosed patients with MM and normal donors were studied. C-C motif chemokine ligand 3 (CCL3) is a cytokine involved in the differentiation of OCs, and its expression is closely related to APRIL (a proliferation-inducing ligand)...
October 28, 2018: Journal of Cellular Biochemistry
Dana E Ward, Brittany L Fay, Adebomi Adejuwon, Huihui Han, Zhengyu Ma
IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is present on all IgE-producing cells, serves as an excellent molecular target for ACT that employs chimeric antigen receptors (CARs)...
2018: Frontiers in Immunology
Sonia Vallet, Julia-Marie Filzmoser, Martin Pecherstorfer, Klaus Podar
Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients' quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition...
October 24, 2018: Pharmaceutics
Bingzong Li, Huiying Han, Sha Song, Gao Fan, Hongxia Xu, Wenqi Zhou, Yingchun Qiu, Chen'ao Qian, Yijing Wang, Zihan Yuan, Yuan Gao, Yongsheng Zhang, Wenzhuo Zhuang
The characteristics of mesenchymal stromal cells (MSCs) which derived from multiple myeloma (MM) patients is typically impaired in osteogenic differentiation. However, the underlying molecular mechanisms need to be further investigated. Long noncoding RNAs (lncRNAs) are emerging as critical regulation molecules in oncogenic pathways. In this study, we identified that bioactive lncRNA HOXC-AS3, which is transcribed in opposite to HOXC10, was presented in MSCs derived from bone marrow (BM) of MM patients (MM-MSCs)...
October 23, 2018: Stem Cells
Utkarsh Painuly, Vijay Ramakrishnan, Teresa Kimlinger, Linda Wellik, Jessica Haug, Wilson Gonsalves, Lintao Bi, Zhongxia Huang, S Vincent Rajkumar, Shaji Kumar
Aberrant expression of proteins involved in cell division is a constant feature in multiple myeloma (MM), especially in high-risk disease. Increasingly, therapy of myeloma is moving towards individualization based on underlying genetic abnormalities. Aurora kinases are important mediators of cell cycle and are up regulated in MM. Functional loss of Aurora kinases results in genetic instability and dysregulated division leading to cellular aneuploidy and growth arrest. We investigated the role of Aurora kinase inhibition in MM, using a small molecule inhibitor A1014907...
October 2, 2018: Oncotarget
Kun Chen, Jing Fan, Zhao-Fan Luo, Ying Yang, Wen-Jun Xin, Cui-Cui Liu
BACKGROUND: Bortezomib is a frequently used chemotherapeutic drug for the treatment of multiple myeloma and other nonsolid malignancies. Accumulating evidence has demonstrated that bortezomib-induced persistent pain serves as the most frequent reason for treatment discontinuation. METHODS: The von Frey test was performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, western blot, immunohistochemistry, and small interfering RNA were performed to explore the molecular mechanisms in adult male Sprague-Dawley rats...
October 20, 2018: Journal of Neuroinflammation
Dimitrios C Ziogas, Meletios A Dimopoulos, Efstathios Kastritis
Multiple myeloma (MM) is characterized by notable inter-patient and intra-clonal heterogeneity that is gradually decoded over the last decade. Despite the deeper and better understanding of its biology and the development of novel therapeutic strategies that have prolonged overall survival, MM still retains a poor prognosis in patient subgroups with certain high-risk features. Areas covered: This article summarizes currently identified features that stratified patients in high-risk myeloma with impaired prognosis and discusses available therapeutic options that may partially overcome the impact of these adverse factors in patients' outcome...
November 2018: Expert Review of Hematology
Loredana Cappellacci, Diego R Perinelli, Filippo Maggi, Mario Grifantini, Riccardo Petrelli
Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors...
October 16, 2018: Current Medicinal Chemistry
Reeder M Robinson, Leticia Reyes, Ravyn M Duncan, Haiyan Bian, Allen B Reitz, Yefim Manevich, Jesse J McClure, Matthew M Champion, C James Chou, Meahgen E Sharik, Marta Chesi, P Leif Bergsagel, Nathan G Dolloff
Multiple Myeloma (MM) is highly sensitive to disruptions in cellular protein homeostasis. Proteasome inhibitors (PIs) are initially effective in the treatment of MM, although cures are not achievable and the emergence of resistance limits the durability of responses. New therapies are needed for refractory patients, and those that combat resistance to standard of care agents would be particularly valuable. Screening of multiple chemical libraries for PI re-sensitizing compounds identified E61 as a potent enhancer of multiple PIs and MM specific activity...
October 12, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Yuki Fujiwara, Yi Sun, Robert J Torphy, Jiadai He, Katsuhiko Yanaga, Barish H Edil, Richard D Schulick, Yuwen Zhu
Thalidomide-like drugs have been approved for the treatment of human multiple myeloma (MM), with their direct antitumor effects and immunomodulatory functions well documented. However, the exact molecular mechanisms that govern these effects remain unclear. Here we demonstrate that pomalidomide (POM) promotes immune response by inhibiting expression of PD-L1. POM inhibited PD-L1 expression on tumor cells to promote cytotoxic T lymphocyte (CTL) activity in vitro and suppressed PD-L1 upregulation on antigen-presenting cells (APC) to prevent peptide-induced T cell tolerance...
October 12, 2018: Cancer Research
Raman Kumar, Nidhi Gupta, Himani, Alpana Sharma
Shelterin complex and its associated molecules are imperative for proper functioning and maintenance of human telomeres. These molecules in association with human telomerase have been found altered in most cancers including multiple myeloma thereby proposed them as suitable therapeutic targets. Further, due to aggressive and recurring behavior of myeloma novel, efficacious and safe therapeutic agents for disease prevention are primary requirements for treatment of this disease. This maiden attempt evaluated the anti-proliferative properties of tanshinone I (TanI) alone or in combination with lenalidomide (Len) on myeloma cancer cell lines (RPMI8226 and U226)...
October 11, 2018: Molecular Biology Reports
Yingying Wang, Linlin Wu, Haiyan Cai, Hu Lei, Chun-Min Ma, Li Yang, Hanzhang Xu, Qi Zhu, Zhujun Yao, Yingli Wu
Aberrant activation of signal transducer and activator of transcription 3 (STAT3) plays a critical role in the proliferation and survival of multiple myeloma. And inactivation of STAT3 is considered a promising strategy for the treatment of multiple myeloma. Here we show that the sinomenine derivative YL064 could selectively reduce the cell viability of multiple myeloma cell lines and primary multiple myeloma cells. Moreover, YL064 also induces cell death of myeloma cells in the presence of stromal cells. Western blot analysis showed that YL064 inhibited the constitutive activation and IL-6-induced activation of STAT3, reflected by the decreased phosphorylation of STAT3 on Tyr705...
2018: Cell Death Discovery
Adam Levin, Parameswaran Hari, Binod Dhakal
Significant advancements have been made in the molecular mechanisms of myelomagenesis, diagnostic methods, prognostication, and the treatment options in multiple myeloma (MM) over the last decade. Despite these, MM remains a heterogeneous disease with differing outcomes. As myeloma treatment landscape continues to expand, personalized treatment that provides maximum benefit to a specific patient becomes more important. In the last few years, serum monoclonal proteins including the serum-free light chain assays, imaging, and cytogenetics have been used to predict the outcomes of MM patients receiving different types of therapies...
November 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Yan-Fang Wang, Hua Wang, Lian-Yong Xi, Zhen-Hao Zhang, Jing Wang, Fei Dong, Xiao-Yan Ke
OBJECTIVE: To detect the molecular cytogenetic abnormalities of multiple myeloma (MM) by using microrray-based comparative genomic hybridization (array-CGH) technology and to investigate its value of application in MM. METHODS: The whole-genoine copy number variants (CNV) of bone marrow samples acquired from 20 cases of newly diagnosed MM patients were detected by genome-wide hybridization and scanning by CytoScan 750K Array (Affymetrix). At the same time, the chromosome abnormalities of bone marrow cells were detected by karyotype analysis and FISH using 9 specific probes: D13S319, RB1, p53, 1q21, IgH, IgH/CCND1, IgH/FGFR3, IgH/MAF, IgH/MAFB...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Zsuzsanna Kovacs, Andras Guttman
Multiple myeloma (MM) is characterized as the clonal proliferation of malignant plasma B-lymphocytes and even as of today, it is an incurable disease. MM accounts for approximately 10% of all hematologic cancers. Its molecular pathogenesis is poorly understood, but the bone marrow microenvironment of tumor cells and genetic factors have apparent roles in the process. Accurate diagnosis is important to properly identify and stratify the disease, however, MM identification steps are time-consuming and expensive...
October 8, 2018: Current Molecular Medicine
Ravi K Anchoori, Rosie Jiang, Shiwen Peng, Ruey-Shyang Soong, Aliyah Algethami, Michelle A Rudek, Nicole Anders, Chien-Fu Hung, Xiang Chen, Xiuxiu Lu, Olumide Kayode, Marzena Dyba, Kylie J Walters, Richard B S Roden
Substitution of the m , p -chloro groups of bis-benzylidinepiperidone RA190 for p -nitro, generating RA183, enhanced covalent drug binding to Cys88 of RPN13. Treatment of cancer cell lines with RA183 inhibited ubiquitin-mediated protein degradation, resulting in rapid accumulation of high-molecular-weight polyubiquitinated proteins, blockade of NFκB signaling, endoplasmic reticulum stress, an unfolded protein response, production of reactive oxygen species, and apoptotic cell death. High-grade ovarian cancer, triple-negative breast cancer, and multiple myeloma cell lines were particularly vulnerable to RA183...
September 30, 2018: ACS Omega
Jayeeta Ghose, Domenico Viola, Cesar Terrazas, Enrico Caserta, Estelle Troadec, Jihane Khalife, Emine Gulsen Gunes, James Sanchez, Tinisha McDonald, Guido Marcucci, Balveen Kaur, Michael Rosenzweig, Jonathan Keats, Steven Rosen, Amrita Krishnan, Abhay R Satoskar, Craig C Hofmeister, Flavia Pichiorri
Daratumumab (Dara), a human immunoglobulin G1 kappa (IgG1κ) monoclonal anti-CD38 antibody, has been approved by the U.S. Food and Drug Administration for the treatment of relapsed multiple myeloma (MM) as a single agent as well as in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI). Although the scientific rationale behind the use of Dara in combination with IMiDs has been extensively explored, the molecular mechanisms underlying Dara-PI regimens have not yet been investigated...
2018: Oncoimmunology
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