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https://www.readbyqxmd.com/read/27913523/advances-and-practical-use-of-monoclonal-antibodies-in-multiple-myeloma-therapy
#1
Hans C Lee, Donna M Weber
The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27908965/inf-%C3%AE-encoding-plasmid-administration-triggers-bone-loss-and-disrupts-bone-marrow-microenvironment
#2
Dimitrios Agas, Guilherme Gusmâo Silva, Fulvio Laus, Andrea Marchigiani, Melania Capitani, Cecilia Vullo, Giuseppe Catone, Giovanna Lavava, Antonio Concetti, Luigi Marchetti, Maria Giovanna Sabbieti
IFN-γ is a pleotropic cytokine produced in the bone microenvironment. Although IFN-γ is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN-γ recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN-γ encoding plasmid (pIFN-γ) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis...
December 1, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27907202/a-reproducible-method-for-isolation-and-in-vitro-culture-of-functional-human-lymphoid-stromal-cells-from-tonsils
#3
Yotam E Bar-Ephraim, Tanja Konijn, Mehmet Gönültas, Reina E Mebius, Rogier M Reijmers
The stromal compartment of secondary lymphoid organs is classicaly known for providing a mechanical scaffold for the complex interactions between hematopoietic cells during immune activation as well as for providing a niche which is favorable for survival of lymphocytes. In recent years, it became increasingly clear that these cells also play an active role during such a response. Currently, knowledge of the interactions between human lymphoid stroma and hematopoietic cells is still lacking and most insight is based on murine systems...
2016: PloS One
https://www.readbyqxmd.com/read/27905003/new-agents-in-hsc-mobilization
#4
REVIEW
Mélanie J Domingues, Susan K Nilsson, Benjamin Cao
Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions...
November 30, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27904036/differential-regulation-of-lympho-myelopoiesis-by-stromal-cells-in-the-early-and-late-phases-in-balb-c-mice-repeatedly-exposed-to-lipopolysaccharide
#5
Isao Tsuboi, Tomonori Harada, Yoko Hirabayashi, Jun Kanno, Shin Aizawa
Chronic lipopolysaccharide (LPS) exposure to mice reduces the lymphoid compartment and skews the hematopoietic cell compartment toward myeloid-cells, which is considered to be a direct effect of LPS on hematopoietic stem cells. However, the effect of chronic LPS exposure on stromal-cells, which compose the hematopoietic microenvironment, has not been elucidated. Here, we investigated early- and late-phase effects of repeated LPS exposure on stromal-cells. During the early phase, when mice were treated with 5 or 25 µg LPS three times at weekly intervals, the numbers of myeloid-progenitor (colony forming unit-granulocyte macrophage (CFU-GM)) cells and B lymphoid-progenitor (CFU-preB) cells in the bone-marrow (BM) rapidly decreased after each treatment...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903985/the-tissue-inhibitor-of-metalloproteinases-1-timp-1-promotes-survival-and-migration-of-acute-myeloid-leukemia-cells-through-cd63-pi3k-akt-p21-signaling
#6
Dorian Forte, Valentina Salvestrini, Giulia Corradi, Lara Rossi, Lucia Catani, Roberto M Lemoli, Michele Cavo, Antonio Curti
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899994/targeting-of-the-leukemia-microenvironment-by-c-rgdfv-overcomes-the-resistance-to-chemotherapy-in-acute-myeloid-leukemia-in-biomimetic-polystyrene-scaffolds
#7
Zhao-Hua Shen, Dong-Feng Zeng, Xiao-Yan Wang, Ying-Ying Ma, Xi Zhang, Pei-Yan Kong
The bone marrow microenvironment provides a relative sanctuary from cytotoxic drugs for leukemia cells. The present niche models concentrate on a two-dimensional (2D) co-culture system in vitro, which does not imitate the in vivo environment, while the 3D scaffolds are more reflective of this. Osteopontin (Opn) secreted by bone marrow osteoblasts, may participate in protecting leukemia cells from apoptosis by binding to its receptor αvβ3, which can be expressed on the surface of the leukemia MV4-11 cell line...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895704/the-extracellular-microscape-governs-mesenchymal-stem-cell-fate
#8
REVIEW
William J Hadden, Yu Suk Choi
Each cell forever interacts with its extracellular matrix (ECM); a stem cell relies on this interaction to guide differentiation. The stiffness, nanotopography, protein composition, stress and strain inherent to any given ECM influences stem cell lineage commitment. This interaction is dynamic, multidimensional and reciprocally evolving through time, and from this concerted exchange the macroscopic tissues that comprise living organisms are formed. Mesenchymal stem cells can give rise to bone, cartilage, tendon and muscle; thus attempts to manipulate their differentiation must heed the physical properties of incredibly complex native microenvironments to realize regenerative goals...
2016: Journal of Biological Engineering
https://www.readbyqxmd.com/read/27895645/inflamm-aging-of-hematopoiesis-hematopoietic-stem-cells-and-the-bone-marrow-microenvironment
#9
REVIEW
Larisa V Kovtonyuk, Kristin Fritsch, Xiaomin Feng, Markus G Manz, Hitoshi Takizawa
All hematopoietic and immune cells are continuously generated by hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) through highly organized process of stepwise lineage commitment. In the steady state, HSCs are mostly quiescent, while HPCs are actively proliferating and contributing to daily hematopoiesis. In response to hematopoietic challenges, e.g., life-threatening blood loss, infection, and inflammation, HSCs can be activated to proliferate and engage in blood formation. The HSC activation induced by hematopoietic demand is mediated by direct or indirect sensing mechanisms involving pattern recognition receptors or cytokine/chemokine receptors...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27893746/mast-cells-are-abundant-in-primary-cutaneous-t-cell-lymphomas-results-from-a-computer-aided-quantitative-immunohistological-study
#10
Johanna Eder, Radu Rogojanu, Waltraud Jerney, Friedrich Erhart, Alexander Dohnal, Melitta Kitzwögerer, Georg Steiner, Julia Moser, Franz Trautinger
BACKGROUND: Mast cells (MC) are bone marrow derived haematopoetic cells playing a crucial role not only in immune response but also in the tumor microenvironment with protumorigenic and antitumorigenic functions. The role of MC in primary cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphomas with initial presentation in the skin, is largely unknown. OBJECTIVE: To gain more accurate information about presence, number, distribution and state of activation (degranulated vs...
2016: PloS One
https://www.readbyqxmd.com/read/27893741/downregulation-of-blood-monocyte-hla-dr-in-icu-patients-is-also-present-in-bone-marrow-cells
#11
Valérie Faivre, Anne-Claire Lukaszewicz, Didier Payen
BACKGROUND: The downregulation of blood monocyte HLA-DR expression also occurs in tissue infiltrative cells in a context of acute clinical inflammation, especially sepsis. This context favors the development of secondary infections and results from various mechanisms. Little is known about HLA-DR expression on bone marrow (BM) cells of the monocyte lineage, the source of circulating monocytes. This study analyzed the BM HLA-DR expression in ICU patients compared to BM monocytes from non-ICU patients and to blood monocytes of control healthy donors...
2016: PloS One
https://www.readbyqxmd.com/read/27890927/the-ap-1-transcription-factor-junb-is-essential-for-multiple-myeloma-cell-proliferation-and-drug-resistance-in-the-bone-marrow-microenvironment
#12
F Fan, M H Bashari, E Morelli, G Tonon, S Malvestiti, S Vallet, M Jarahian, A Seckinger, D Hose, L Bakiri, C Sun, Y Hu, C R Ball, H Glimm, M Sattler, H Goldschmidt, E F Wagner, P Tassone, D Jaeger, K Podar
Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly due to the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890297/digesting-the-role-of-bone-marrow-macrophages-on-hematopoiesis
#13
REVIEW
Esther Heideveld, Emile van den Akker
Tissue resident macrophages are found in various tissues like Langerhans cells in the skin or alveolar macrophages in the lung, and their main function is to regulate organ homeostasis. They have also been observed in the bone marrow and these cells in particular have been gaining importance in recent years as they are key players in hematopoiesis. However, as the characterization and classification of these putatively different bone marrow resident macrophages is far from established there is a need to generate an overview of tissue resident macrophages of the bone marrow...
November 17, 2016: Immunobiology
https://www.readbyqxmd.com/read/27889088/osteoblast-cellular-activity-on-low-elastic-modulus-ti-24nb-4zr-8sn-alloy
#14
K C Nune, R D K Misra, S J Li, Y L Hao, R Yang
OBJECTIVES: Low modulus β-titanium alloys with non-toxic alloying elements are envisaged to provide good biocompatibility and alleviate the undesired stress shielding effect. The objective of this study is to fundamentally elucidate the biological response of novel high strength-low elastic modulus Ti2448 alloy through the study of bioactivity and osteoblast cell functions. METHODS: Characterization techniques such as SEM, EDX, XRD, and fluorescence microscopy were utilized to analyze the microstructure, morphology, chemical composition, and cell adhesion...
November 23, 2016: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/27888521/cancer-associated-mesenchymal-stroma-fosters-the-stemness-of-osteosarcoma-cells-in-response-to-intratumoral-acidosis-via-nf-%C3%AE%C2%BAb-acivation
#15
Sofia Avnet, Gemma Di Pompo, Tokuhiro Chano, Costantino Errani, Arig Ibrahim-Hashim, Robert J Gillies, Davide Maria Donati, Nicola Baldini
The role of mesenchymal stem cells (MSC) in osteosarcoma (OS), the most common primary tumor of bone, has not been extensively elucidated. We have recently shown that OS is characterized by interstitial acidosis, a microenvironmental condition that is similar to a wound setting, in which mesenchymal reactive cells are activated to release mitogenic and chemotactic factors. We therefore intended to test the hypothesis that, in OS, acid-activated MSC influence tumor cell behavior. Conditioned media or co-culture with normal MSC previously incubated with short-term acidosis (pH 6...
November 26, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27886253/cxcr4-cxcl12-axis-counteracts-hematopoietic-stem-cell-exhaustion-through-selective-protection-against-oxidative-stress
#16
Yanyan Zhang, Mallorie Dépond, Liang He, Adlen Foudi, Edward Owusu Kwarteng, Evelyne Lauret, Isabelle Plo, Christophe Desterke, Philippe Dessen, Nobutaka Fujii, Paule Opolon, Olivier Herault, Eric Solary, William Vainchenker, Virginie Joulin, Fawzia Louache, Monika Wittner
Hematopoietic stem cells (HSCs) undergo self-renewal to maintain hematopoietic homeostasis for lifetime, which is regulated by the bone marrow (BM) microenvironment. The chemokine receptor CXCR4 and its ligand CXCL12 are critical factors supporting quiescence and BM retention of HSCs. Here, we report an unknown function of CXCR4/CXCL12 axis in the protection of HSCs against oxidative stress. Disruption of CXCR4 receptor in mice leads to increased endogenous production of reactive oxygen species (ROS), resulting in p38 MAPK activation, increased DNA double-strand breaks and apoptosis leading to marked reduction in HSC repopulating potential...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27885781/cellular-response-of-osteoblasts-to-low-modulus-ti-24nb-4zr-8sn-alloy-mesh-structure
#17
K C Nune, R D K Misra, S J Li, Y L Hao, R Yang
Titanium alloys (Ti-6Al-4V and Ti-6Al-7Nb) are widely used for implants, which are characterized by high elastic modulus (∼110 GPa) with (α + β) structure and that may induce undesirable stress shielding effect and immune responses associated with the presence of toxic elements. In this regard, we have combined the attributes of a new alloy design and the concept of additive manufacturing to fabricate 3D scaffolds with an interconnected porous structure. The new alloy is a β-type Ti-24Nb-4Zr-8Sn (Ti2448) alloy with significantly reduced modulus...
November 25, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27884971/progression-in-patients-with-low-and-intermediate1-risk-del-5q-myelodysplastic-syndromes-is-predicted-by-a-limited-subset-of-mutations
#18
Christian Scharenberg, Valentina Giai, Andrea Pellagatti, Leonie Saft, Marios Dimitriou, Monica Jansson, Martin Jädersten, Alf Grandien, Iyadh Douagi, Donna S Neuberg, Katarina LeBlanc, Jacqueline Boultwood, Mohsen Karimi, Sten Eirik W Jacobsen, Petter S Woll, Eva Hellström-Lindberg
A high proportion of patients with lower-risk del(5q) myelodysplastic syndromes (MDS) will respond to treatment with lenalidomide. Median duration of transfusion-independence is 2 years with some long-lasting responses, but almost 40% of patients progress to acute leukemia by 5 years after start of treatment. Mechanisms underlying disease progression other than the well-established finding of small TP53-mutated subclones at diagnosis remain unclear. We studied a longitudinal cohort of 35 low- and intermediate-1-risk del(5q) patients treated with lenalidomide (n=22) or not (n=13) by flow cytometric surveillance of hematopoietic stem and progenitor cells (HSPC) subsets, targeted sequencing of mutational patterns, and changes in the bone marrow microenvironment...
November 24, 2016: Haematologica
https://www.readbyqxmd.com/read/27881474/cancer-secretome-may-influence-bsp-and-dsp-expression-in-human-salivary-gland-cells
#19
Samantha Lynn Hamilton, Blake Ferando, Asha Sarah Eapen, Jennifer Chian Yu, Anita Rose Joy
One of the biggest challenges in managing head and neck cancers, especially salivary gland cancers, is the identification of secreted biomarkers of the disease that can be evaluated noninvasively. A relevant source of enriched tumor markers could potentially be found in the tumor secretome. Although numerous studies have evaluated secretomes from various cancers, the influence of the cancer secretome derived from salivary gland cancers on the behavior of normal cells has not yet been elucidated. Our data indicate that secretome derived from salivary gland cancer cells can influence the expression of two potential biomarkers of oral cancer-namely, bone sialoprotein (BSP) and dentin sialoprotein (DSP)-in normal salivary gland cells...
November 23, 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27873175/mobilization-of-human-immature-hematopoietic-progenitors-through-combinatory-use-of-bortezomib-and-immunomodulatory-drugs
#20
Taro Tochigi, Takatoshi Aoki, Yoshikane Kikushige, Tomohiko Kamimura, Yoshikiyo Ito, Takahiro Shima, Takuji Yamauchi, Yasuo Mori, Goichi Yoshimoto, Kenjiro Kamezaki, Koji Kato, Katsuto Takenaka, Hiromi Iwasaki, Koichi Akashi, Toshihiro Miyamoto
Combination use of the proteasome inhibitor bortezomib and the immunomodulatory drugs lenalidomide or thalidomide has provided superior outcomes in multiple myeloma over their single use; however, these combinations can produce significant toxicities. Unexpectedly, we found a small but significant increase in the population of immature granulocytes and erythrocytes/megakaryocytes in peripheral blood in 16 of 22 patients (73%) treated with dexamethasone in combination with bortezomib and immunomodulatory drugs (triplet), but not in any of 25 patients treated with either bortezomib or immunomodulatory drugs with dexamethasone (doublet)...
November 21, 2016: International Journal of Hematology
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