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Molecular myeloma

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https://www.readbyqxmd.com/read/29049036/histone-deacetylase-inhibitor-bg45-mediated-ho-1-expression-induces-apoptosis-of-multiple-myeloma-cells-by-the-jak2-stat3-pathway
#1
Sishi Tang, Bingqing Cheng, Nana Zhe, Dan Ma, Jibing Xu, Xinyao Li, Yongling Guo, Weibing Wu, Jishi Wang
Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro...
October 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29045072/cell-signaling-model-connects-vorinostat-pharmacokinetics-and-tumor-growth-response-in-multiple-myeloma-xenografts
#2
Charvi Nanavati, Donna Ruszaj, Donald E Mager
Multiple myeloma is a fatal hematological malignancy with high rates of drug resistance and relapse. Vorinostat, a histone deacetylase inhibitor, has shown promise in enhancing efficacy when combined with current myeloma therapies. In this study, temporal changes of critical proteins and cell proliferation were measured in myeloma cells exposed to vorinostat. A model linking biomarker dynamics to cell proliferation was developed that captured vorinostat effects on signal transduction and cell viability. The model structure and parameters were fixed to describe tumor dynamics in vivo, and tumor-specific growth and death rate parameters were estimated...
October 17, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29039470/effects-of-baicalein-on-proliferation-apoptosis-migration-and-invasion-of-ewing-s-sarcoma-cells
#3
Conglin Ye, Xiaolong Yu, Jin Zeng, Min Dai, Bin Zhang
Ewing's sarcoma (ES) is a rare tumor that is more frequent in pediatric and adolescent age groups. In the past few decades, long-term survival in affected patients has improved due to the success of multimodal therapy. However, long-term survival is inevitably restricted by the late side-effects of chemotherapy. Besides, early metastasis also contributes to the poor prognosis of ES. Recently, traditional Chinese medicines (TCMs) have increasingly attracted interest due to the promising clinical results and fewer side-effects for the treatment of cancers...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29036218/crystallographic-and-thermodynamic-characterization-of-phenylaminopyridine-bisphosphonates-binding-to-human-farnesyl-pyrophosphate-synthase
#4
Jaeok Park, Dmitry Rodionov, Joris W De Schutter, Yih-Shyan Lin, Youla S Tsantrizos, Albert M Berghuis
Human farnesyl pyrophosphate synthase (hFPPS) catalyzes the production of the 15-carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the mevalonate pathway and a well-established drug target. Notably, it was elucidated as the molecular target of nitrogen-containing bisphosphonates, a class of drugs that have been widely successful against bone resorption disorders. More recently, research has focused on the anticancer effects of these inhibitors. In order to achieve increased non-skeletal tissue exposure, we created phenylaminopyridine bisphosphonates (PNP-BPs) that have bulky hydrophobic side chains through a structure-based approach...
2017: PloS One
https://www.readbyqxmd.com/read/29025286/-thalidomide-therapy-in-relapsed-diffuse-large-b-cell-lymphoma-in-elderly-patients-three-cases
#5
Nikolett Wohner, Gergely Varga, Péter Szloboda, Péter Farkas, András Masszi, Laura Horváth, Gergely Szombath, Judit Várkonyi, Szabolcs Benedek, Tamás Masszi
Diffuse large B-cell lymphoma (DLBCL), a high-grade lymphoproliferative disease, is the most common lymphoma in adults, representing 31% of non-Hodgkin lymphomas (NHL). In elderly patients treatment is problematic because of the high toxicity of standard chemotherapy protocols, especially in relapsed cases, where high-dose chemotherapy and haematopoietic stem cell transplantation would be the best choice. More and more data is becoming available on alternative treatment of refractory/relapsed NHL, including studies on the positive effect of thalidomide and second generation IMiDs in DLBCL, which are already part of the standard treatment protocol in myeloma multiplex and myelodysplasia...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28987930/impact-of-new-drugs-on-the-long-term-follow-up-of-upfront-tandem-auto-allo-transplant-in-multiple-myeloma
#6
Luisa Giaccone, Andrea Evangelista, Francesca Patriarca, Roberto Sorasio, Massimo Pini, Fabrizio Carnevale-Schianca, Moreno Festuccia, Lucia Brunello, Francesco Zallio, Enrico Maffini, Paola Omedé, Sara Bringhen, Nicola Mordini, Renato Fanin, Giovannino Ciccone, Mario Boccadoro, Benedetto Bruno
Prior to the introduction of "new drugs", we designed a trial where 162 newly diagnosed myeloma patients were biologically randomized to receive either an autograft (auto-SCT) followed by a non-myeloablative allograft (allo-SCT) or a double auto-SCT. Fifty-eight patients in the allo-SCT arm and 46 in the double auto-SCT arm completed the assigned treatment. At median follow-up of 12.3 years from allo-SCT and 12.1 years from second auto-SCT, median overall survival (OS) was 11.4 in the allo-SCT arm and 3.9 years in the auto-SCT -arm (p=0...
October 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28978849/therapeutic-approach-for-relapsed-refractory-multiple-myeloma-the-logic-and-practice
#7
Junya Kuroda
The long-term outcome of multiple myeloma (MM) has been greatly improved by the advent of new agents such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), despite the disease remaining mostly incurable. Treatment design is the critical determinant for the survival period and for the quality and way of life in patients with relapsed/refractory MM (RRMM). Recently, the choice of therapeutic options for RRMM has been expanded by the introduction of second generation PIs such as carfilzomib and ixazomib, and therapeutic monoclonal antibodies such as elotuzumab and daratumumab...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28966941/increased-expression-of-the-tight-junction-protein-tjp1-zo-1-is-associated-with-upregulation-of-taz-tead-activity-and-an-adult-tissue-stem-cell-signature-in-carfilzomib-resistant-multiple-myeloma-cells-and-high-risk-multiple-myeloma-patients
#8
Irene Riz, Robert G Hawley
Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomib- and carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfz-like phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature...
July 2017: Oncoscience
https://www.readbyqxmd.com/read/28961309/phase-ii-study-of-bortezomib-cyclophosphamide-and-dexamethasone-as-induction-therapy-in-multiple-myeloma-dsmm-xi-trial
#9
Hermann Einsele, Monika Engelhardt, Christoph Tapprich, Jürgen Müller, Peter Liebisch, Christian Langer, Martin Kropff, Lars O Mügge, Wolfram Jung, Hans-Heinrich Wolf, Bernd Metzner, Christina Hart, Martin Gramatzki, Bernd Hertenstein, Michael Pfreundschuh, Wolf Rösler, Thomas Fischer, Georg Maschmeyer, Lothar Kanz, Georg Hess, Elke Jäger, Martin Bentz, Heinz A Dürk, Hans Salwender, Holger Hebart, Christian Straka, Stefan Knop
We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis...
September 29, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28944848/cmip-is-oncogenic-in-human-gastric-cancer-cells
#10
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/28943924/network-based-analysis-of-the-molecular-mechanisms-of-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance
#11
Zhi Liu, Jing Huang, Qi Zhong, Yanling She, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to reveal the molecular mechanisms of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). This was a secondary study on microarray dataset GSE80608, downloaded from the Gene Expression Omnibus database, which included 10 control samples, 10 MGUS samples and 10 MM samples. Differentially expressed genes (DEGs) were identified between control and MGUS samples, and between control and MM samples. A protein-protein interaction (PPI) network was built for studying the interactions between the DEGs...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28931820/the-non-canonical-poly-a-polymerase-fam46c-acts-as-an-onco-suppressor-in-multiple-myeloma
#12
Seweryn Mroczek, Justyna Chlebowska, Tomasz M Kuliński, Olga Gewartowska, Jakub Gruchota, Dominik Cysewski, Vladyslava Liudkovska, Ewa Borsuk, Dominika Nowis, Andrzej Dziembowski
FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#13
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C - X - C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
September 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28913874/an-algorithmic-approach-to-diagnose-haematolymphoid-neoplasms-in-effusion-by-combining-morphology-immunohistochemistry-and-molecular-cytogenetics
#14
L Chen, J S Zhang, D G Liu, D Cui, Z L Meng
OBJECTIVE: There are limited studies of cytology diagnosis of haematopoietic and lymphoid tumours in serosal effusion except for occasional case reports. We would like to demonstrate an algorithmic approach for accurate diagnosis, especially in patients without previous history. METHODS: We reviewed 36 cases of lymphoma diagnosed in serosal effusion following an algorithmic approach. Suspected tumour cells were classified into small, intermediate and large sizes and two characteristic forms of plasmacytoid and Reed Sternberg-like on smears (step 1), followed by utilising panels of immunohistochemical markers and Epstein-Barr encoding region in situ hybridisation on cell blocks (step 2)...
September 15, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/28903567/minimal-residual-disease-assessment-in-multiple-myeloma-by-multiparametric-flow-cytometry
#15
L Rihova, P Vsianska, R Bezdekova, R Kralova, M Penka, M Krejci, L Pour, R Hájek
BACKGROUND: Progress in treatment of multiple myeloma extensively increased patient remission rates, so minimal residual disease (MRD) detection becomes essential to assess the effectivity of treatment and depth of complete response. Nowadays, multiparametric flow cytometry (MFC) is the most used method for monitoring of MRD presence in the bone marrow of multiple myeloma patients; however, detection on molecular level can be used as well. It is evident that choice of protocol used for MFC-MRD assessment can significantly affect required results; nevertheless, standardized and highly sensitive approach of "next generation flow" is already available...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903565/liquid-biopsies-the-clinics-and-the-molecules
#16
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
https://www.readbyqxmd.com/read/28894561/solitary-plasmacytoma
#17
REVIEW
Sara Grammatico, Emilia Scalzulli, Maria Teresa Petrucci
Solitary plasmacytoma is a rare disease characterized by a localized proliferation of neoplastic monoclonal plasma cells, without evidence of systemic disease. It can be subdivided into solitary bone plasmacytoma if the lesion originates in bone, or solitary extramedullary plasmacytoma if the lesion involves a soft tissue. The incidence of solitary bone plasmacytoma is higher than solitary extramedullary plasmacytoma. Also, the prognosis is different: even if both forms respond well to treatment, overall survival and progression-free survival of solitary bone plasmacytoma are poorer than solitary extramedullary plasmacytoma due to its higher rate of evolution in multiple myeloma...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28856086/identification-of-novel-targets-for-multiple-myeloma-through-integrative-approach-with-monte-carlo-cross-validation-analysis
#18
Congjian Liu, Xiang Gu, Zhenxian Jiang
More than one pathway is involved in disease development and progression, and two or more pathways may be interconnected to further affect the disease onset, as functional proteins participate in multiple pathways. Thus, identifying cross-talk among pathways is necessary to understand the molecular mechanisms of multiple myeloma (MM). Based on this, this paper looked at extracting potential pathway cross-talk in MM through an integrative approach using Monte Carlo cross-validation analysis. The gene expression library of MM (accession number: GSE6477) was downloaded from the Gene Expression Omnibus (GEO) database...
September 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/28841203/high-sensitivity-blood-based-m-protein-detection-in-scr-patients-with-multiple-myeloma
#19
J R Mills, D R Barnidge, A Dispenzieri, D L Murray
We assessed the ability of a mass spectrometry-based technique, called monoclonal immunoglobulin rapid accurate mass measurement (miRAMM), to extend the analytical range of M-protein detection in serum samples obtained from myeloma patients in stringent complete response (sCR) post-autologous stem cell transplant (ASCT). To aid the M-protein detection post ASCT, the accurate molecular mass of the M-protein light chain at diagnosis was determined in all patients (N=30) and used to positively identify clones in the sCR serum...
August 25, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28840415/endothelial-progenitor-cells-in-multiple-myeloma-neovascularization-a-brick-to-the-wall
#20
REVIEW
Maria Margarida Tenreiro, Maria Leonor Correia, Maria Alexandra Brito
Multiple myeloma (MM) is characterized by the clonal expansion of plasma cells in the bone marrow that leads to events such as bone destruction, anaemia and renal failure. Despite the several therapeutic options available, there is still no effective cure, and the standard survival is up to 4 years. The evolution from the asymptomatic stage of monoclonal gammopathy of undetermined significance to MM and the progression of the disease itself are related to cellular and molecular alterations in the bone marrow microenvironment, including the development of the vasculature...
August 24, 2017: Angiogenesis
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