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Molecular myeloma

Z Faraahi, M Baud'huin, P I Croucher, C Eaton, M A Lawson
Multiple myeloma (MM) is characterised by destructive lytic bone disease, caused by induction of bone resorption and impaired bone formation. Our understanding of the molecular mechanisms responsible for osteoblast suppression, are limited. Using the 5T2MM murine model of MM we have previously shown that suppression of the activity of a known inhibitor of bone formation Dikkopf-1 (Dkk1) prevents the development of lytic bone disease. Here we have demonstrated that another potential inhibitor of bone formation, sclerostin domain containing 1 (Sostdc1) is expressed at low levels in MM and osteoblast lineage cells when these cells are grown separately in cell culture but its expression is significantly induced in both cell types when these cells are in contact...
February 15, 2019: Bone
Akira Iwamoto, Yuichi Inoue, Hirofumi Tachibana, Hiroharu Kawahara
We found that strawberry (Fragaria x ananassa) extract has an IgE production suppressive activity and its oral administration improved skin manifestation in atopic dermatitis model mice. In present study, we identified an active substance using the IgE-producing human myeloma cell line U266. Gel filtration experiment indicated that the IgE suppressor was more than 6 kDa in molecular size. In addition, its pectinase treatment inhibited the activity, suggesting that the active substance in strawberry extract is pectin...
February 15, 2019: Cytotechnology
Harmen van Andel, Kinga A Kocemba, Marcel Spaargaren, Steven T Pals
Aberrant activation of Wnt/β-catenin signaling plays a central role in the pathogenesis of a wide variety of malignancies and is typically caused by mutations in core Wnt pathway components driving constitutive, ligand-independent signaling. In multiple myelomas (MMs), however, these pathway intrinsic mutations are rare despite the fact that most tumors display aberrant Wnt pathway activity. Recent studies indicate that this activation is caused by genetic and epigenetic lesions of Wnt regulatory components, sensitizing MM cells to autocrine Wnt ligands and paracrine Wnts emanating from the bone marrow niche...
February 15, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
M Žárska, D Vrábel, R Bezdekova, M Štork, M Jarošová, Z Adam, M Krejčí, L Pour, S Ševčíková
BACKGROUND: Plasma cell leukemia (PCL) is a rare dis-ease and possibly the most aggressive form of monoclonal gammopathy. It is classified into two forms -  primary PCL that occurs without a previously identifiable multiple myeloma stage, and secondary PCL that develops from previously dia-gnosed multiple myeloma. These two forms have different cytogenetic and molecular profiles, but both forms have an aggressive clinical course. Combinations of different therapeutic approaches includ-ing autologous stem cell transplantation and currently proteasome inhibitors and immunomodulatory drugs are used to treat PCL...
2019: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Akhand Pratap Singh, Rachna Singh, Sumit Singh Verma, Vipin Rai, Catherine H Kaschula, Pralay Maiti, Subash Chandra Gupta
Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis...
February 11, 2019: Medicinal Research Reviews
Dickran Kazandjian, Elizabeth Hill, Malin Hultcrantz, Evan H Rustad, Venkata Yellapantula, Theresia Akhlaghi, Neha Korde, Sham Mailankody, Alex Dew, Elli Papaemmanuil, Irina Maric, Mary Kwok, Ola Landgren
Caucasian Americans (CA) compared with African Americans (AA) have a twofold increased incidence of multiple myeloma (MM) and have an earlier age of diagnosis. However, there is sparse information regarding underlying biological differences across racial/ethnic groups. We characterized genetic alterations using a targeted next-generation sequencing assay called myTYPE, developed at MSKCC, allowing capture of somatic mutations, IgH translocations, gains/losses, and hyperdiploidy. Samples were obtained from the NIH Plasma Cell Dyscrasia Racial Disparity Cohort...
February 4, 2019: Blood Cancer Journal
Vaishali Aggarwal, Dharambir Kashyap, Katrin Sak, Hardeep Singh Tuli, Aklank Jain, Ashun Chaudhary, Vivek Kumar Garg, Gautam Sethi, Mukerrem Betul Yerer
Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas...
February 2, 2019: International Journal of Molecular Sciences
Jill Corre, Hervé Avet-Loiseau
Although therapeutic strategies have been adapted to age and comorbidities of myeloma patients for a long time, all patients currently experiment the same treatment whatever their genomic risk. However, high-risk patients should benefit right now from the most efficient drugs combinations. Herein, we review and discuss how to optimally define risk to adapt treatment and why a modern multiparametric definition of genomic risk is urgently needed. Minimal residual disease status will probably also take a growing place in patient's management, including in treatment adaptation...
January 2019: Cancer Journal
Ajay K Nooka, Sagar Lonial
Over the last 2 decades, thalidomide analogs have induced significant antimyeloma effects via immune-modulation, antiangiogenesis and antiproliferative effects. While the exact molecular mechanism of the targets or the mediators of thalidomide activity were not known, a seminal discovery of cereblon as a thalidomide-binding protein led to explaining the mechanistic basis of antimyeloma activity for this class of agents. Identification of the mechanisms of resistance for immunomodulatory agents (IMiDs), which will have significant clinical implications, remains poorly understood...
January 2019: Cancer Journal
Eduardo Silva-Pavez, Paulina Villar, César Trigo, Esteban Caamaño, Ignacio Niechi, Pablo Pérez, Juan P Muñoz, Francisco Aguayo, Verónica A Burzio, Manuel Varas-Godoy, Ariel F Castro, María I Colombo, Julio C Tapia
Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal cancer (CRC) patients. On the other hand, mTORC1 plays an important role in the regulation of protein synthesis, cell growth, and autophagy. Some studies suggest that CK2 regulates mTORC1 in several cancers...
January 25, 2019: Cell Death & Disease
Kari Högstrand, Jessica M Lindvall, Anne Sundblad, Alf Grandien
An experimental system where defined alterations in gene function or gene expression levels in primary B cells would result in the development of transformed plasma cells in vitro would be useful in order to facilitate studies of the underlying molecular mechanisms of plasma cell malignancies. Here, such a system is described in which primary murine B cells rapidly become transformed into surface CD138+ , IgM-/low , CD19- IgM-secreting plasma cells as a result of expression of the transcription factors IRF4 and MYC together with simultaneous expression of BMI1, mutated p53 or silencing of p19Arf , and suppression of intrinsic apoptosis through expression of BCLXL...
January 21, 2019: European Journal of Immunology
Gilbert Gastelum, Eric Y Chang, David Shackleford, Nicholas Bernthal, Jeffery Kraut, Kevin Francis, Victoria Smutko, Patrick Frost
Multiple myeloma (MM) tumors engraft in the bone marrow (BM) and their survival and progression are dependent upon complex molecular and cellular interactions that exist within this microenvironment. Yet the BM microenvironment cannot be easily replicated in vitro, which potentially limits the physiologic relevance of many in vitro and ex vivo experimental models. These issues can be overcome by utilizing a xenograft model in which luciferase (LUC)-transfected 8226 MM cells will specifically engraft in the mouse skeleton...
January 7, 2019: Journal of Visualized Experiments: JoVE
Emilie Chalayer, Brigitte Tardy-Poncet, Lionel Karlin, Céline Chapelle, Aurélie Montmartin, Michèle Piot, Denis Guyotat, Philippe Collet, Thomas Lecompte, Bernard Tardy
Background: Multiple myeloma (MM) is associated with a high risk of thrombosis, particularly during the first months of treatment including immunomodulatory drugs (IMiDs). There is no consensus on prevention of thromboembolic risk in patients with de novo MM, and identification of patients requiring anticoagulant thromboprophylaxis remains challenging. Evaluating coagulability by an in vitro thrombin generation (TG) test might be a way of identifying such patients. Objective: To determine whether TG assessment could reveal an increase in coagulability during the first three chemotherapy cycles...
January 2019: Research and Practice in Thrombosis and Haemostasis
Jiaqi Chen, Yongli Ying, Hongjun Zhu, Tingjun Zhu, Chunsheng Qu, Jinhong Jiang, Bingmu Fang
Curcumin, a polyphenol derived from the rhizome of Curcuma , is a potential tumor inhibitor through affecting signaling pathways and epigenetic regulation. The mammalian target of rapamycin (mTOR) gene serves a crucial role in the carcinogenesis of multiple myeloma. The curcumin-induced epigenetic regulation of mTOR, including promoter DNA methylation in multiple myeloma, has not yet been fully elucidated. In the present study, antitumor effects of curcumin were investigated in RPMI-8226 and NCI-H929 cells using an MTT assay and flow cytometry...
January 2019: Oncology Letters
Giao N Lê, Jonathan Bones, Mark Coyne, Despina Bazou, Paul Dowling, Peter O'Gorman, Anne-Marie Larkin
Multiple myeloma, an incurable malignancy of the plasma cells in the bone marrow, has a complex pathogenesis due to clonal heterogeneity. Over the years, many clinical trials and researches have led to the development of effective myeloma treatments, resulting in survival prolongation. Molecular prognostic markers for risk-stratification to predict survival, and predictive markers for treatment response are being extensively explored. This review discusses the current risk-adaptive strategies based on genetic and molecular risk signatures that are in practice to predict survival and describes the future prognostic and predictive biomarkers across the fields of genomics, proteomics, and glycomics in myeloma...
January 17, 2019: Molecular omics
Tian-Ze Ma, Zhe Piao, Sheng-Yu Jin, Yong-Geun Kwak
The exact cause instigating multiple myeloma (MM) has not been fully elucidated, and the disease has a median survival of 6 months without any treatment. To identify potential biomarkers of MM, serum proteins reflecting alteration in their proteomes were analyzed in 6 patients with MM compared with 6 healthy controls using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of flight mass spectrometry. The most notable differentially expressed proteins were validated by immunoblotting and changes in mRNA expression were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR)...
January 2019: Experimental and Therapeutic Medicine
Guoqiang Huang, Xiaopeng Liu, Xiaoying Zhao, Jing Zhao, Jinxia Hao, Juan Ren, Ying Chen
MiR-9 has been reported to play a pivotal role in multiple human cancers through acting as an oncogene or tumor suppressor. In this study, we explored the possible role and molecular mechanism of miR-9 in multiple myeloma (MM). MiR-9 expression was examined by qRT-PCR assay. Transfection with miR-9-mimics, miR-9-inhibitor, pcDNA-TRIM56 or si-TRIM56 into cells was used to change the expression levels of miR-9 and TRIM56. Western blot analysis was used to detect the expression of TRIM56, p65, p-p65, IκBα and p-IκBα...
January 14, 2019: Cell Biology International
Weilong Zhang, Ying Song, Xue He, Xiaoni Liu, Ye Zhang, Zuozhen Yang, Ping Yang, Jing Wang, Kai Hu, Weiyou Liu, Xiuru Zhang, Xiaoliang Yuan, Hongmei Jing
Plasma cell myeloma (PCM) secretes monoclonal immunoglobulin (Ig) by clonal plasma cells of abnormal proliferation in the bone marrow. As PCM is incurable, it is necessary to find new biomarkers to predict the prognosis and recurrence of PCM. The relationship between cancer and RBBP8 has not been fully studied. The role of RBBP8 in tumorigenesis remains inconsistent. We described the expression of RBBP8 in the gene expression profile of 1930 PCM samples (1878 PCM patients) from seven independent data sets. We analyzed the relationship between RBBP8 and survival prognosis, recurrence, and treatment response in patients with PCM, and the biological significance of RBBP8 in PCM...
January 9, 2019: Cancer Gene Therapy
Jin Sung Jang, Ying Li, Amit Kumar Mitra, Lintao Bi, Alexej Abyzov, Andre J van Wijnen, Linda B Baughn, Brian Van Ness, Vincent Rajkumar, Shaji Kumar, Jin Jen
We used single cell RNA-Seq to examine molecular heterogeneity in multiple myeloma (MM) in 597 CD138 positive cells from bone marrow aspirates of 15 patients at different stages of disease progression. 790 genes were selected by coefficient of variation (CV) method and organized cells into four groups (L1-L4) using unsupervised clustering. Plasma cells from each patient clustered into at least two groups based on gene expression signature. The L1 group contained cells from all MGUS patients having the lowest expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathways (p < 1...
January 3, 2019: Blood Cancer Journal
Soichiro Endo, Takahiro Yamada, Yasunori Naganawa, Toshihiro Tabuchi, Hiroshi Shinmoto
Peripheral blood lymphocytes from a patient allergic to Japanese cedar pollens were transformed by Epstein-Barr virus infection. Some transformed B-lymphoblastoid cells (BLCs) secreted IgM class antibodies to cedar pollen extracts and tomato fruit extracts. One stable human-mouse hybridoma clone Y-22-3-3 secreting IgM class monoclonal antibody to tomato fruit extracts was established by cell fusion of BLCs with mouse myeloma cells. Western blot analysis of tomato extracts showed Y-22-3-3 monoclonal antibody recognized a tomato protein with a molecular weight of 40 kDa...
December 28, 2018: Human Antibodies
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