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Bone microenvironment

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https://www.readbyqxmd.com/read/28550626/combination-breast-cancer-chemotherapy-with-doxorubicin-and-cyclophosphamide-damages-bone-and-bone-marrow-in-a-female-rat-model
#1
Chiaming Fan, Kristen R Georgiou, Howard A Morris, Ross A McKinnon, Dorothy M K Keefe, Peter R Howe, Cory J Xian
PURPOSE: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. METHODS: This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. RESULTS: AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase...
May 26, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28549419/fluorescent-cxcr4-targeting-peptide-as-alternative-for-antibody-staining-in-ewing-sarcoma
#2
Laurens G L Sand, Tessa Buckle, Fijs W B van Leeuwen, Willem E Corver, Alwine B Kruisselbrink, Aart G Jochemsen, Pancras C W Hogendoorn, Károly Szuhai
BACKGROUND: Ewing sarcoma is an aggressive, highly metastatic primary bone and soft tissue tumor most frequently occurring in the bone of young adolescents. Patients, especially those diagnosed with a metastatic disease, have a poor overall survival. Chemokine receptor CXCR4 has a key pro-tumorigenic role in the tumor microenvironment of Ewing sarcoma and has been suggested to be involved in the increased metastatic propensity. Earlier studies on CXCR4 protein expression in Ewing sarcoma yielded contradictory results when compared to CXCR4 RNA expression studies...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28548004/reduced-cellularity-of-bone-marrow-in-multiple-sclerosis-with-decreased-msc-expansion-potential-and-premature-ageing-in-vitro
#3
Juliana Redondo, Pamela Sarkar, Kevin Kemp, Paul F Virgo, Joya Pawade, Aimie Norton, David C Emery, Martin G Guttridge, David I Marks, Alastair Wilkins, Neil J Scolding, Claire M Rice
BACKGROUND: Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. OBJECTIVES: To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. METHODS: Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28544348/galectin-1-promotes-an-m2-macrophage-response-to-polydioxanone-scaffolds
#4
Daniel Abebayehu, Andrew Spence, Barbara D Boyan, Zvi Schwartz, John J Ryan, Michael J McClure
Regulating soft tissue repair to prevent fibrosis and promote regeneration is central to creating a microenvironment conducive to soft tissue development. Macrophages play an important role in this process. Their response can be modulated using biomaterials, altering cytokine and growth factor secretion to promote regeneration. Electrospun polydioxanone (PDO) fiber scaffolds promoted an M2 phenotype when macrophages were cultured on large diameter, highly porous scaffolds, but an M1 phenotype on smaller diameter fibers...
May 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28537457/inhibition-of-mtor-kinase-as-a-therapeutic-target-for-acute-myeloid-leukemia
#5
Yoko Tabe, Agostino Tafuri, Kazumasa Sekihara, Haeun Yang, Marina Konopleva
Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a therapeutic challenge. The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is one of the key aberrant intracellular axes involved in AML. Areas covered: mTOR plays a critical role in sensing and responding to environmental determinants such as nutrient availability, stress, and growth factor concentrations; and in modulating key cellular functions such as proliferation, metabolism, and survival...
May 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28536320/-stress-response-mechanism-in-hematopoietic-stem-cells
#6
Keiyo Takubo
At steady state, hematopoietic stem cells(HSCs), the most undifferentiated cells in the hematological system, are kept quiescent in the cell cycle. Upon hematological stresses, including radiation, anti-cancer medication, infection, and transplantation, bone marrow HSCs enter the cell cycle and robustly repopulate the entire hematopoietic system via multi-lineage differentiation and self-renewal, partly due to the alteration of their surrounding microenvironment or niche. Such hematological repopulation activity is termed "stress hematopoiesis," an activity essential for homeostatic maintenance of blood production...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28536276/persistent-immune-stimulation-exacerbates-genetically-driven-myeloproliferative-disorders-via-stromal-remodeling
#7
Claudio Tripodo, Alessia Burocchi, Pier Paolo Piccaluga, Claudia Chiodoni, Paola Portararo, Barbara Cappetti, Laura Botti, Alessandro Gulino, Alessandro Isidori, Arcangelo Liso, Giuseppe Visani, Maria Paola Martelli, Brunangelo Falini, Pier Paolo Pandolfi, Mario P Colombo, Sabina Sangaletti
Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with down-regulation of SPARC and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28534514/integration-of-hypoxic-hif-%C3%AE-signaling-in-blood-cancers
#8
REVIEW
L Schito, S Rey, M Konopleva
Hypoxia (low O2) is a fundamental microenvironmental determinant of bone marrow (BM) pathophysiology. Recent data from molecular and clinical studies indicate that hematopoiesis and leukemogenesis are dependent upon hypoxia-inducible factors (HIFs), a family of essential transcriptional activators mediating the metazoan hypoxic response. In blood cancers, the synergism between HIF overexpression and stabilization within the hypoxic BM microenvironment promotes disease progression, therapy resistance and relapse...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534212/breast-cancer-metastasis-putative-therapeutic-role-of-vascular-cell-adhesion-molecule-1
#9
REVIEW
Rohit Sharma, Rohini Sharma, Tejinder Pal Khaket, Chanchala Dutta, Bornisha Chakraborty, Tapan Kumar Mukherjee
BACKGROUND: Breast cancer is a notable cause of cancer-related death in women worldwide. Metastasis to distant organs is responsible for ~90% of this death. Breast cells convert to malignant cancer cells after acquiring the capacity of invasion/intravasation into surrounding tissues and, finally, extravasation/metastasis to distant organs (i.e., lymph nodes, lungs, bone, brain). Metastasis to distant organs depends on interactions between disseminated tumor cells (DTCs) and the endothelium of blood vessels present in the tumor microenvironment...
May 22, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28534115/complexity-of-bone-marrow-hematopoietic-stem-cell-niche
#10
REVIEW
Noboru Asada, Shoichiro Takeishi, Paul S Frenette
Hematopoietic stem cells (HSCs) that produce a variety of hematopoietic lineage cells throughout the life reside in specialized microenvironment called "niche" in the bone marrow (BM) where they are tightly regulated. With the recent advances in experimental technologies enabling the selective deletion of molecules, various types of cells in the BM have been proposed to contribute to HSC niche activity. Among these are stromal cells closely associated with the vasculature. In this review, we provide an overview of recent advances in HSC niche research, and focus on the studies describing the functional roles of perivascular cells for HSC maintenance and mobilization...
May 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28533307/sox11-promotes-tumor-protective-microenvironment-interactions-through-cxcr4-and-fak-regulation-in-mantle-cell-lymphoma
#11
Patricia Balsas, Jara Palomero, Álvaro Eguileor, Marta Leonor Rodriguez, Maria Carmela Vegliante, Ester Planas-Rigol, Marta Sureda-Gómez, Maria C Cid, Elias Campo, Virginia Amador
SOX11 overexpression in Mantle Cell Lymphoma (MCL) has been associated with more aggresive behavior and worse outcome. However, SOX11 oncogenic pathways driving MCL tumor progression are poorly known. Here, we demonstrate that SOX11 binds to regulatory regions of two important genes for microenvironment-signals in cancer, (C-X-C motif) chemokine receptor 4 (CXCR4) and PTK2 (encoding for focal adhesion kinase (FAK)). Moreover, SOX11-positive xenograft and human primary MCL tumors overexpress cell migration and stromal stimulation gene signatures compared to their SOX11-negative counterparts...
May 22, 2017: Blood
https://www.readbyqxmd.com/read/28531915/bone-marrow-stem-cells-anti-liver-fibrosis-potency-inhibition-of-hepatic-stellate-cells-activity-and-extracellular-matrix-deposition
#12
Ervina Julien Sitanggang, Radiana Dhewayani Antarianto, Sri Widia A Jusman, Jeanne Adiwinata Pawitan, Ahmad Aulia Jusuf
Transplantation of bone marrow derived stem cells (BMSCs) has been reported inhibits liver fibrosis. Several in vitro studies by co-culturing BMSCs and hepatic stellate cells (HSCs) indirectly or directly in 2D models showed inhibition of HSC as the key player in liver fibrosis. In this study, we investigated direct effect of BMSCs on HSCs by co-culturing BMSCs and HSCs in 3D model as it represents the liver microenvironment with intricate cell-cell and cell-matrix interactions. Primary isolated rat HSCs and BMSCs were directly co-cultured at 1:1 ratio with hanging drop method...
May 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28531804/protective-effect-and-mechanism-of-lycopene-on-endothelial-progenitor-cells-epcs-from-type-2-diabetes-mellitus-rats
#13
Yao-Chi Zeng, Li-Sheng Peng, Liyuan Zou, Shu-Fen Huang, Yi Xie, Gui-Ping Mu, Xue-Hui Zeng, Xi-Lin Zhou, Ya-Chi Zeng
Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528673/acid-sensing-ion-channel-pharmacology-past-present-and-future-%C3%A2
#14
Lachlan D Rash
pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28527581/nuclear-receptors-in-skeletal-homeostasis
#15
Hao Zuo, Yihong Wan
Nuclear receptors are a family of transcription factors that can be activated by lipophilic ligands. They are fundamental regulators of development, reproduction, and energy metabolism. In bone, nuclear receptors enable bone cells, including osteoblasts, osteoclasts, and osteocytes, to sense their dynamic microenvironment and maintain normal bone development and remodeling. Our views of the molecular mechanisms in this process have advanced greatly in the past decade. Drugs targeting nuclear receptors are widely used in the clinic for treating patients with bone disorders such as osteoporosis by modulating bone formation and resorption rates...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527187/quantitative-stereological-analysis-of-the-highly-porous-hydroxyapatite-scaffolds-using-x-ray-cm-and-sem
#16
Justyna Zygmuntowicz, Aneta Zima, Joanna Czechowska, Karol Szlazak, Anna Ślosarczyk, Katarzyna Konopka
BACKGROUND: Material properties of the scaffolds as well as their microstructure are vital in determining in vivo cellular response. Three-dimensional (3D), highly porous scaffolds are used in tissue engineering to provide a suitable microenvironment and to support regeneration of bone. Both pore sizes and their architecture, in particular interconnection density, impact functionality of scaffold during its biomedical applications. OBJECTIVE: In this paper a comparative study of the microstructure of highly porous hydroxyapatite scaffolds produced via gelcasting of foamed slurries and replication of polyurethane sponge were carried out...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#17
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28523251/bone-marker-gene-expression-in-calvarial-bones-different-bone-microenvironments
#18
Osama Al-Amer
BACKGROUND: In calvarial mice, mesenchymal stem cells (MSCs) differentiate into osteoprogenitor cells and then differentiate into osteoblasts that differentiate into osteocytes, which become embedded within the bone matrix. In this case, the cells participating in bone formation include MSCs, osteoprogenitor cells, osteoblasts and osteocytes. The calvariae of C57BL/KaLwRijHsD mice consist of the following five bones: two frontal bones, two parietal bones and one interparietal bone. This study aimed to analyse some bone marker genes and bone related genes to determine whether these calvarial bones have different bone microenvironments...
December 2017: Journal of Biological Research
https://www.readbyqxmd.com/read/28521202/dual-growth-factor-loaded-nonmulberry-silk-fibroin-carbon-nanofiber-composite-3d-scaffolds-for-in%C3%A2-vitro-and-in%C3%A2-vivo-bone-regeneration
#19
Deboki Naskar, Ananta K Ghosh, Mahitosh Mandal, Piyali Das, Samit K Nandi, Subhas C Kundu
In recent years the potential application of nanocomposite biomaterials in tissue engineering field is gaining importance because of the combined features of all the individual components. A bottom-up approach is acquired in this study to recreate the bone microenvironment. The regenerated silk protein fibroin obtained from nonmulberry tropical tasar Antheraea mylitta species is reinforced with functionalized carbon nano fiber (CNF) and the composite sponges are fabricated using facile green aqueous based method...
May 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28516389/microenvironmental-scenario-of-the-bone-marrow-of-inorganic-arsenic-exposed-experimental-mice
#20
Jacintha Archana Pereira, Sujata Law
Exposure to arsenic on a regular basis, mainly through drinking water, agricultural pesticide, and sometimes therapeutic dose, results in various diseases of different tissues including the bone marrow hematopoietic system. Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally mature blood cells by the support of microenvironmental components. The present study has been aimed to understand stem cell microenvironmental status during arsenic toxicity and the consequent reflection of dysregulation involving the hematopoietic machinery in experimental mice...
May 17, 2017: Biological Trace Element Research
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