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Molecular myeloma

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https://www.readbyqxmd.com/read/29456245/animal-models-of-monoclonal-immunoglobulin-related-renal-diseases
#1
REVIEW
Christophe Sirac, Guillermo A Herrera, Paul W Sanders, Vecihi Batuman, Sebastien Bender, Maria V Ayala, Vincent Javaugue, Jiamin Teng, Elba A Turbat-Herrera, Michel Cogné, Guy Touchard, Nelson Leung, Frank Bridoux
The renal deposition of monoclonal immunoglobulins can cause severe renal complications in patients with B cell and plasma cell lymphoproliferative disorders. The overproduction of a structurally unique immunoglobulin can contribute to the abnormal propensity of monoclonal immunoglobulins to aggregate and deposit in specific organs. A wide range of renal diseases can occur in multiple myeloma or monoclonal gammopathy of renal significance, including tubular and glomerular disorders with organized or unorganized immunoglobulin deposits...
February 19, 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29448111/in-silico-screening-of-proteins-targeting-circulating-mirnas-for-improved-diagnosis-of-multiple-myeloma
#2
Shradha Suyal, Manish Pratap Singh, Himanshu Shekhar, Sameer Srivastava
Multiple Myeloma (MM) is a B-cell malignancy, which is characterized by the expansion of clonal plasma cells in the bone marrow, leading to abnormal accumulation of monoclonal antibodies in circulation. Certain circulating miRNAs are deregulated in MM and their differential expression profiles in body fluids can be quantified and used discriminate between the premalignant and malignant stages of MM. Our study identifies protein which would show affinity for a selected panel of circulating miRNAs deregulated in MM...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29424538/development-of-a-targeted-mass-spectrometry-serum-assay-to-quantify-m-protein-in-the-presence-of-therapeutic-monoclonal-antibodies
#3
Marina Zajec, Joannes F M Jacobs, Patricia J T A Groenen, Corrie M de Kat Angelino, Christoph Stingl, Theo M Luider, Yolanda B De Rijke, Martijn M VanDuijn
M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab and nivolumab)...
February 9, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29416605/human-dkk1-and-human-hsp70-fusion-dna-vaccine-induces-an-effective-anti-tumor-efficacy-in-murine-multiple-myeloma
#4
Ting-Ting Liu, Yang Wu, Ting Niu
Dickkopf-1 (DKK1) is an ideal target for the immunotherapy of multiple myeloma. Heat Shock protein70 (HSP70) is a class of important molecular chaperone to promote antigen presentation. Homologous xenogeneic antigens can enhance immunogenicity and induce stronger anti-tumor immune response than that of allogeneic ones. Therefore, we constructed human DKK1 and human HSP70 DNA fusion vaccine (hDKK1-hHSP70), and then determined its anti-tumor immuno- genicity and anti-tumor effects on immunizing BALB/c mice already inoculated with NS-1 murine multiple myeloma cells in prophylactic and therapeutic models using cytotoxic T lymphocytes, enzyme-lined immunosorbent assay, flow cytometry, immunohistochemistry and Hochest staining...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29393672/functional-and-molecular-mri-of-the-bone-marrow-in-multiple-myeloma
#5
Vassilis Koutoulidis, Nickolas Papanikolaou, Lia A Moulopoulos
MRI plays an important role in the management of patients with plasma cell neoplasms and has been recognized as a biomarker of malignancy in the novel criteria for the diagnosis of multiple myeloma. Functional and molecular MRI techniques such as Diffusion-Weighted Imaging (Spinal or Whole Body), Intravoxel Incoherent Motion, and Dynamic Contrast-Enhanced MRI, provide additional information related to tumor cellularity and angiogenesis, which may have prognostic implications for patients with smoldering and symptomatic myeloma...
February 2, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29377227/lymphoproliferative-disorders-in-patients-with-chronic-myeloproliferative-neoplasms-a-systematic-review
#6
Monia Marchetti, Alessandra Carobbio, Enrica Capitoni, Tiziano Barbui
Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. In order to systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%) or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous...
January 27, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29372735/isolation-of-circulating-plasma-cells-from-blood-of-patients-diagnosed-with-clonal-plasma-cell-disorders-using-cell-selection-microfluidics
#7
Joyce W Kamande, Maria A M Lindell, Małgorzata A Witek, Peter M Voorhees, Steven A Soper
Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0...
January 26, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29365400/-effects-of-psmb5-on-proliferation-and-bortezomib-chemo-resistance-in-human-myeloma-cells-and-its-related-molecular-mechanisms
#8
H M Mo, Q Y Wu, D Y Han, R Liu, X Ma, P Zhou, K L Xu
Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29334316/potential-therapeutic-and-economic-value-of-risk-stratified-treatment-as-initial-treatment-of-multiple-myeloma-in-europe
#9
Jennifer G Gaultney, Therese W Ng, Carin A Uyl-de Groot, Pieter Sonneveld, Erik H van Beers, Martin H van Vliet, William K Redekop
Biomarkers associated with prognosis in multiple myeloma (MM) can be used to stratify patients into risk categories. An attractive alternative to uniform treatment (UT), risk-stratified treatment (RST) is proposed where high-risk patients receive bortezomib-based regimens while standard-risk patients receive alternative less costly regimens. An early Markov-type decision analytic model evaluated the potential therapeutic and economic value of different RST strategies compared with UT in MM patients in key European countries...
January 15, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29330358/pathogenesis-of-bone-disease-in-multiple-myeloma-from-bench-to-bedside
#10
REVIEW
Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Meletios A Dimopoulos
Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process...
January 12, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29327711/cd3-positive-plasmablastic-b-cell-neoplasms-a-diagnostic-pitfall
#11
Zenggang Pan, Mingyi Chen, Qianyun Zhang, Endi Wang, Liqun Yin, Youyuan Xu, Qin Huang, Youzhong Yuan, Xiaohui Zhang, Gang Zheng, Ji Yuan
Rare B-cell neoplasms with plasmablastic differentiation may aberrantly express CD3 by immunohistochemical staining, which places a great challenge for diagnosis. We here studied 17 cases of CD3+ plasmablastic B-cell neoplasms, including 12 plasmablastic lymphomas and 5 plasmablastic plasma cell myelomas. All 17 cases occurred in the extranodal sites with a male predominance (13/17). Four cases were initially misinterpreted by outside institutions, among which three were diagnosed as 'peripheral T-cell lymphoma, not otherwise specified' and one was classified as 'poorly differentiated neuroendocrine carcinoma'...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29326121/modeling-multiple-myeloma-bone-marrow-interactions-and-response-to-drugs-in-a-3d-surrogate-microenvironment
#12
Daniela Belloni, Silvia Heltai, Maurilio Ponzoni, Antonello Villa, Barbara Vergani, Lorenza Pecciarini, Magda Marcatti, Stefania Girlanda, Giovanni Tonon, Fabio Ciceri, Federico Caligaris-Cappio, Marina Ferrarini, Elisabetta Ferrero
Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma-bone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electron-microscopic analyses, engaged contacts with stromal cells and endothelial cells...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29307099/boolean-network-modeling-in-systems-pharmacology
#13
Peter Bloomingdale, Van Anh Nguyen, Jin Niu, Donald E Mager
Quantitative systems pharmacology (QSP) is an emerging discipline that aims to discover how drugs modulate the dynamics of biological components in molecular and cellular networks and the impact of those perturbations on human pathophysiology. The integration of systems-based experimental and computational approaches is required to facilitate the advancement of this field. QSP models typically consist of a series of ordinary differential equations (ODE). However, this mathematical framework requires extensive knowledge of parameters pertaining to biological processes, which is often unavailable...
January 6, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29301798/enhanced-elimination-of-cyclophosphamide-by-high-cut-off-haemodialysis-single-dose-pharmacokinetics-in-a-patient-with-cast-nephropathy
#14
Gabriele Eden, W Nikolaus Kühn-Velten, Carsten Hafer, Jan T Kielstein
High cut-off (HCO) haemodialysis removes free light chains in patients with multiple myeloma. This is possible as HCO dialysers allow clearance of molecules up to a molecular weight of 65 kDa. In contrast, high-flux dialysers, which are used in routine haemodialysis, only remove molecules up to a molecular weight of 20 kDa. Even though patients with advanced myeloma frequently need dialysis and alkylating agents, drug dosing recommendations in this patient population are scarce at best or absent as for cyclophosphamide dosing in patients with myeloma undergoing HCO dialysis...
January 4, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29296798/a-phase-2-study-of-panobinostat-with-lenalidomide-and-weekly-dexamethasone-in-myeloma
#15
Ajai Chari, Hearn J Cho, Amishi Dhadwal, Gillian Morgan, Lisa La, Katarzyna Zarychta, Donna Catamero, Erika Florendo, Nadege Stevens, Daniel Verina, Elaine Chan, Violetta Leshchenko, Alessandro Laganà, Deepak Perumal, Anna Huo-Chang Mei, Kaity Tung, Jami Fukui, Sundar Jagannath, Samir Parekh
Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290968/inhibition-of-ezh2-triggers-the-tumor-suppressive-mir-29b-network-in-multiple-myeloma
#16
Maria Angelica Stamato, Giada Juli, Enrica Romeo, Domenica Ronchetti, Mariamena Arbitrio, Daniele Caracciolo, Antonino Neri, Pierosandro Tagliaferri, Pierfrancesco Tassone, Nicola Amodio
Downregulation of tumor suppressor (TS) microRNAs (miRNAs) commonly occurs in human cancer, including multiple myeloma (MM). We previously demonstrated that miR-29b is a relevant TS miRNA, whose expression in MM cells is inhibited by HDAC4-dependent deacetylation. Here, we provide novel insights into epigenetic mechanisms suppressing miR-29b in MM. In MM patient-derived plasma cells, we found inverse correlation between miR-29b and EZH2 mRNA expression. Both siRNAs and pharmacologic inhibitors of EZH2 led to miR-29b upregulation, and this effect was ascribed to reduced H3K27-trimethylation (H3K27me3) of miR-29a/b-1 promoter regions...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286493/twenty-five-years-of-the-national-academy-of-medical-sciences-of-ukraine-progress-and-priorities-for-future-of-radiation-medicine-and-biology
#17
D Bazyka
After the creation of the Academy of Medical Sciences of Ukraine in 1993 the Research Center for Radiation Medicine was among the first institutions to join the Academy (fig. 1). Estab lishing the Academy was among the first steps of the independent Ukrainian government and aimed to provide a high level health care for population. It was extremely needed for the minimization of Chornobyl medical consequences. This choice was related to a growing recognition of the scientific research in fulfilling the Сenter's mission - study of the effects of low dose radiation on human body and radiation protection of the exposed population...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29278963/a-plasma-cell-myeloma-with-post-therapy-anaplastic-morphology-osteomyelosclerosis-and-strong-pan-cytokeratin-ae1-ae3-expression-a-potential-diagnostic-pitfall
#18
Vani Bharani, Prashant Sharma, Amanjit Bal, Gaurav Prakash
Reactive and neoplastic plasma cells can display considerable morphological anaplasia as well as variable immunoreactivity for epithelial markers including epithelial membrane antigen, pan-cytokeratin (panCK) and high-molecular-weight cytokeratin, potentially creating diagnostic dilemmas. We describe the case of a 51-year-old male, previously treated for IgGλ plasma cell myeloma, whose bone marrow biopsy showed focal replacement by sheets of pleomorphic malignant cells and grade 3 myelofibrosis, raising the morphological possibility of a carcinomatous infiltration...
December 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29260980/baohuoside-i-suppresses-cell-proliferation-and-migration-by-up-regulating-mir-144-in-melanoma
#19
Ya-Guang Peng, Li Zhang
CONTEXT: Baohuoside-I was reported to induce apoptosis in non-small-cell lung cancer and inhibit the growth of multiple myeloma cells. The antitumour potential of baohuoside-I has not been demonstrated in melanoma yet. OBJECTIVE: To investigate the potential antitumour activity of baohuoside-I against melanoma and elucidate its underlying molecular mechanism. MATERIALS AND METHODS: Cell viability was evaluated by MTT assay. The malignant invasion capacity was measured with trans-well assay...
December 2018: Pharmaceutical Biology
https://www.readbyqxmd.com/read/29259189/milder-degenerative-effects-of-carfilzomib-vs-bortezomib-in-the-drosophila-model-a-link-to-clinical-adverse-events
#20
Eleni N Tsakiri, Evangelos Terpos, Eleni-Dimitra Papanagnou, Efstathios Kastritis, Vincent Brieudes, Maria Halabalaki, Tina Bagratuni, Bogdan I Florea, Herman S Overkleeft, Luca Scorrano, Alexios-Leandros Skaltsounis, Meletios A Dimopoulos, Ioannis P Trougakos
Proteasome inhibitors, e.g. Bortezomib (BTZ) and Carfilzomib (CFZ), have demonstrated clinical efficacy against haematological cancers. Interestingly, several adverse effects are less common, compared to BTZ, in patients treated with CFZ. As the molecular details of these observations remain not well understood we assayed the pathophysiological effects of CFZ vs. BTZ in the Drosophila experimental model. Mass Spectrometry analyses showed that neither CFZ nor BTZ are hydrolysed in flies' tissues, while at doses inducing similar inhibition of the rate limiting for protein breakdown chymotrypsin-like (CT-L) proteasomal activity, CFZ treatment resulted in less intense increase of oxidative stress or activation of antioxidant and proteostatic modules...
December 19, 2017: Scientific Reports
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