F Gulli, M Marino, C Napodano, K Pocino, F Pandolfi, A Gasbarrini, G L Rapaccini, U Basile
OBJECTIVE: Chronic Hepatitis C virus (HCV) infection can cause severe extrahepatic manifestations, such as mixed cryoglobulins (MC), up to the development of B cell nonHodgkin's lymphoma (B-NHL). Mechanisms transforming of HCV infection into lymphoproliferative and/or autoimmune disorders are still poorly understood. In course of HCV infection, the sustained virus-driven antigenic stimulation may probably induce a B-cell clonal expansion. Measurements of serum free light chains (FLCs) levels, considered as a direct marker of B cell activity, are analyzed with increasing interest in clinical practice, for diagnosis, monitoring and follow-up of plasma cell dyscrasia...
August 2020: European Review for Medical and Pharmacological Sciences
James W Murphy, Deepa Rajasekaran, Janie Merkel, Erin Skeens, Camille Keeler, Michael E Hodsdon, George P Lisi, Elias Lolis
CXCL12 activates CXCR4 and is involved in embryogenesis, hematopoiesis, and angiogenesis. It has pathological roles in HIV-1, WHIM disease, cancer, and autoimmune diseases. An antagonist, AMD3100, is used for the release of CD34+ hematopoietic stem cells from the bone marrow for autologous transplantation for lymphoma or multiple myeloma patients. Adverse effects are tolerated due to its short-term treatment, but AMD3100 is cardiotoxic in clinical studies for HIV-1. In an effort to determine whether Saccharomyces cerevisiae expressing a functional human CXCR4 could be used as a platform for identifying a ligand from a library of less ∼1,000 compounds, a high-throughput screening was developed...
2020: Frontiers in Molecular Biosciences
Fahd Refai, Wafaey Gomaa, Layla Abdullah
Plasmacytomas of the thyroid gland are rare, whether or not they arise as solitary (primary) lesions or secondary to systemic multiple myeloma. Here, we present the case of a 71-year-old female presenting with goiter and Hashimoto's thyroiditis, in whom the subsequent histopathological diagnosis of plasmacytoma was a surprise. In presenting this case, we summarize the last 25 years of literature on thyroid plasmacytoma and review the salient clinicopathological characteristics, differential diagnoses, management, and outcomes of this rare condition...
April 2020: Journal of Microscopy and Ultrastructure
Shivesh Maharaj, Sheetal Mungul
Multiple myeloma is a biologically diverse, malignant disease that involve plasma cells. Multiple myeloma is characterized by the unrestrained proliferation of monoclonal plasma cells within the bone marrow. In the present case report, the case of a human immunodeficiency virus (HIV) positive patient with an initial manifestation of extramedullary myeloma involving the parotid gland is described. The patient had been on antiretrovirals for the last two years. A Medline, Embase, Scopus and Google Scholar search was performed using the key words: 'Parotid extramedullary myeloma AND HIV' as part of the literature review...
October 2020: Biomedical Reports
Kyungwoo Lee, Su Hwa Jang, Hong Tian, Sun Jung Kim
Proper expression of the transcription factor, Positive regulatory domain 1 ( PRDM1 ), is required for maintaining homeostasis of human monocyte derived-dendritic cells (MO-DCs). The molecular mechanisms and gene targets of PRDM1 in B and T lymphocytes have been identified. However, the function of PRDM1 in dendritic cells (DCs) remains unclear. We investigate co-regulators of PRDM1 in MO-DCs identified by mass spectrometry (MS) and co-immunoprecipitation (Co-IP). Notably, non-POU domain-containing octamer-binding protein (NonO) was found to be a PRDM1 binding protein in the nucleus of MO-DCs...
2020: Frontiers in Immunology
Chong Wang, Mengya Li, Shujuan Wang, Zhongxing Jiang, Yanfang Liu
Background: Although assertion that long non-coding RNA (lncRNA) exerts crucial functions in the progression of multiple myeloma (MM) is well documented, few studies investigate function and underlying mechanism of long intergenic non-protein coding RNA 665 (LINC00665) in MM. Patients and Methods: A total of 25 MM patient samples and 15 healthy volunteer samples were collected, and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expressions of LINC00665...
2020: OncoTargets and Therapy
Stefania Raimondo, Ornella Urzì, Alice Conigliaro, Lavinia Raimondi, Nicola Amodio, Riccardo Alessandro
Increasing evidence indicates that extracellular vesicles (EVs) released from both tumor cells and the cells of the bone marrow microenvironment contribute to the pathobiology of multiple myeloma (MM). Recent studies on the mechanisms by which EVs exert their biological activity have indicated that the non-coding RNA (ncRNA) cargo is key in mediating their effect on MM development and progression. In this review, we will first discuss the role of EV-associated ncRNAs in different aspects of MM pathobiology, including proliferation, angiogenesis, bone disease development, and drug resistance...
August 5, 2020: Non-Coding RNA
Michael T Sheehan, Robert A Wermers, Aminah Jatoi, Charles L Loprinzi, Adedayo A Onitilo
Hypercalcemia of malignancy develops in approximately 20-30% of patients with advanced cancer and is an ominous sign. This condition is subdivided into three categories: i) humoral hypercalcemia of malignancy (80% of cases), mediated by systemic parathyroid hormone-related protein; ii) osteolytic metastases (20% of cases), mediated by inflammatory cytokines locally released by tumor cells and/or peri-tumor macrophages; and iii) ectopic production of 1,25-dihydroxyvitamin D (<1% of cases), leading to intestinal hyperabsorption of calcium and increased osteoclastic bone resorption...
July 30, 2020: Medical Hypotheses
Dominik Golicki, Katarzyna Jaśkowiak, Alicja Wójcik, Katarzyna Młyńczak, Iwona Dobrowolska, Andżelika Gawrońska, Grzegorz Basak, Emilian Snarski, Malwina Hołownia-Voloskova, Michał Jakubczyk, Maciej Niewada
OBJECTIVES: We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies. METHODS: The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found...
July 2020: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Samrat Roy Choudhury, Cody Ashby, Ruslana Tytarenko, Michael Bauer, Yan Wang, Shayu Deshpande, Judith Den, Carolina Schinke, Maurizio Zangari, Sharmilan Thanendrarajan, Faith E Davies, Frits van Rhee, Gareth J Morgan, Brian A Walker
BACKGROUND: Multiple Myeloma (MM) is a hematological malignancy with genomic heterogeneity and poor survival outcome. Apart from the central role of genetic lesions, epigenetic anomalies have been identified as drivers in the development of the disease. METHODS: Alterations in the DNA methylome were mapped in 52 newly diagnosed MM (NDMM) patients of six molecular subgroups and matched with loci-specific chromatin marks to define their impact on gene expression. Differential DNA methylation analysis was performed using DMAP with a ≥10% increase (hypermethylation) or decrease (hypomethylation) in NDMM subgroups, compared to control samples, considered significant for all the subsequent analyses with p<0...
August 6, 2020: Journal of Hematology & Oncology
Vien Phan, Tomoki Ito, Muneo Inaba, Yoshiko Azuma, Kayoko Kibata, Noriko Inagaki-Katashiba, Akihiro Tanaka, Atsushi Satake, Shosaku Nomura
Immunomodulatory drugs (IMiDs), lenalidomide and pomalidomide, are widely used treatments for multiple myeloma; however, they occasionally lead to episodes of itchy skin and rashes. Here, we analyzed the effects of IMiDs on human myeloid dendritic cells (mDCs) as major regulators of Th1 or Th2 responses and the role they play in allergy. We found that lenalidomide and pomalidomide used at clinical concentrations did not affect the survival or CD86 and OX40-ligand expression of blood mDCs in response to lipopolysaccharide (LPS) and thymic stromal lymphopoietin (TSLP) stimulation...
August 11, 2020: Blood Advances
John R Rinker, William R Meador, Peter King
Background: Disability accumulation in progressive multiple sclerosis (MS) results from inflammatory and neurodegenerative mechanisms. In animal models of MS, lithium acts to reduce inflammatory demyelination, and in models of neurodegenerative diseases, lithium also slows neuronal death. Prospective studies of lithium in MS patients have not been previously undertaken. Objective: To determine the tolerance and feasibility of using low-dose (150-300 mg/daily) lithium as a pharmaceutical intervention in a cohort of subjects with progressive MS, and to gauge preliminary effects of lithium on change in brain volume over time...
July 2020: Heliyon
Sahrish Ilyas, Pranatharthi H Chandrasekar
Prevention strategies against varicella zoster infection include chemoprophylaxis with acyclovir and live attenuated zoster vaccine. However, resistance to acyclovir has been problematic, and safety concerns have limited the use of the live attenuated vaccine in immunosuppressed patients. Recombinant zoster vaccine, made available in 2017 for the immunocompetent host, has been evaluated for safety, immunogenicity, and efficacy in several immunocompromised settings as well. The present review compares the live attenuated vaccine and the recombinant zoster vaccine and highlights data on the use of recombinant zoster vaccine in different immunocompromised states...
July 2020: Open Forum Infectious Diseases
Hasna Hamdaoui, Abdelhafid Natiq, Oumaima Benlarroubia, Thomas Liehr, Hind Dehbi, Latifa Loukhmas, Fatima Chegdani
Cytogenetic and iFISH plays a major part in the diagnosis of the MM and have an important prognostic significance. 10-15% of patients with amyloidosis will also have multiple myeloma (MM). Few studies have addressed the clinical and cytogenetic features of patients with AL amyloidosis with concurrent multiple myeloma. This study of MM case in which we found a near tetraploid complex karyotype with the t(11;14) (q13;q32) abnormality in cytogenetic analysis and the presence of t(4;14) and del(17p) by iFISH, referred to several studies which showed the translocation t(11;14) as the most frequent abnormality in both AL amyloidosis and MM...
2020: Leukemia Research Reports
Xiaomeng Li, Ning Wu, Wenjie Zhang, Ying Liu, Yue Ming
Background: Both bone metastases and multiple myeloma (MM) are malignant diseases that can appear osteolytic on imaging and are difficult to differentiate. While positron emission tomography/computed tomography (PET/CT) has been demonstrated useful for the diagnosis of various bone lesions, correlations between PET/CT and histopathology and these diseases are unclear. This retrospective study investigated the optimal cutoff standardized uptake value (SUV) to differentiate MM and bone metastasis...
October 2020: Journal of Bone Oncology
Jiadai Xu, Yifeng Sun, Jifeng Jiang, Zhao Xu, Jing Li, Tianhong Xu, Peng Liu
Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138+ cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21)...
2020: Frontiers in Immunology
Lavinia Raimondi, Angela De Luca, Simona Fontana, Nicola Amodio, Viviana Costa, Valeria Carina, Daniele Bellavia, Stefania Raimondo, Sergio Siragusa, Francesca Monteleone, Riccardo Alessandro, Milena Fini, Gianluca Giavaresi
Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression; therefore, targeting of UPR-related molecules may open novel therapeutic avenues. Endoplasmic reticulum (ER) stress and UPR pathways are constitutively activated in MM cells, which are characterized by an increased protein turnover as a consequence of high production of immunoglobulins and high rates of protein synthesis...
August 4, 2020: Cancers
Jean-Pascal Capp, Régis Bataille
The standard model of multiple myeloma (MM) relies on genetic instability in the normal counterparts of MM cells. MM-induced lytic bone lesions are considered as end organ damages. However, bone is a tissue of significance in MM and bone changes could be at the origin/facilitate the emergence of MM. We propose the tissue disruption-induced cell stochasticity (TiDiS) theory for MM oncogenesis that integrates disruption of the microenvironment, differentiation, and genetic alterations. It starts with the observation that the bone marrow endosteal niche controls differentiation...
August 4, 2020: Cancers
Jiro Kikuchi, Yusuke Furukawa
Multiple myeloma (MM) is among the most intractable of malignancies and is characterized by uncontrolled growth of malignant plasma cells in the bone marrow (BM). Elucidation of the mechanisms underlying cell adhesion-mediated drug resistance (CAM-DR) may prolong remission and ultimately improve the survival of MM patients. Toward this goal, we identified trimethylation of histone H3 at lysine-27 (H3K27me3) as a critical histone modification associated with CAM-DR. Cell adhesion counteracted drug-induced hypermethylation of H3K27 via inhibiting phosphorylation of enhancer of zeste homolog 2 (EZH2), and promoted sustained expression of anti-apoptotic genes...
2020: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Naoki Hosen
Integrins play an important role in the homing, survival, proliferation, and drug resistance of multiple myeloma (MM) cells in the bone marrow. Among the many integrin families, the integrins α4β1 (VLA-4) and α4β7 have been reported to have important functions in MM cells. Previous studies have also reported that the three-dimensional structure of an integrin changes depending on its activation state; however, the conformations of integrins expressed in MM cells have not been studied so far. We recently observed that integrin α4β7 constitutively adopts an active conformation in MM cells, and chimeric antigen receptor (CAR) T cell therapy that targets the activated conformation of integrin β7 is a promising new treatment for MM...
2020: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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