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Bone marrow microenvironment

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https://www.readbyqxmd.com/read/29332538/role-of-infiltrating-monocytes-in-the-development-of-radiation-induced-pulmonary-fibrosis
#1
Angela M Groves, Carl J Johnston, Jacqueline P Williams, Jacob N Finkelstein
Lung exposure to radiation induces an injury response that includes the release of cytokines and chemotactic mediators; these signals recruit immune cells to execute inflammatory and wound-healing processes. However, radiation alters the pulmonary microenvironment, dysregulating the immune responses and preventing a return to homeostasis. Importantly, dysregulation is observed as a chronic inflammation, which can progress into pneumonitis and promote pulmonary fibrosis; inflammatory monocytes, which are bone marrow derived and express CCR2, have been shown to migrate into the lung after radiation exposure...
January 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29331301/marrow-adipose-tissue-imaging-in-humans
#2
Vibha Singhal, Miriam A Bredella
Bone strength is affected not only by bone mineral density (BMD) and bone microarchitecture but also its microenvironment. Recent studies have focused on the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss. Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone marrow and many osteoporotic states, including aging, medication use, immobility, over - and undernutrition are associated with increased marrow adiposity. Advancements in imaging technology allow the non-invasive quantification of MAT...
January 10, 2018: Bone
https://www.readbyqxmd.com/read/29331104/inhibition-of-mircorna-34a-enhances-survival-of-human-bone-marrow-mesenchymal-stromal-stem-cells-under-oxidative-stress
#3
Yang Liu, Xiaohu Zhang, Jie Chen, Tingyu Li
BACKGROUND Mesenchymal stromal/stem cells (MSCs) are broadly used for many diseases, but the efficacy of MSC engraftment is very low due to low viability and high cell death rate under a stressful microenvironment. The present study aimed to investigate whether microRNA-34a (miR-34a), which is a downstream target of P53, is involved in H2O2-induced MSC cell death. MATERIAL AND METHODS Human bone marrow MSCs (hMSCs) were purchased from Lonza and were cultured as previously described. hMSCs were transfected with miR-34a inhibitor and exposed to H2O2...
January 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29328867/glioma-stem-cell-niches-in-human-glioblastoma-are-periarteriolar
#4
Vashendriya V V Hira, Diana A Aderetti, Cornelis J F van Noorden
Survival of primary brain tumor (glioblastoma) patients is seriously hampered by glioma stem cells (GSCs) that are distinct therapy-resistant self-replicating pluripotent cancer cells. GSCs reside in GSC niches, which are specific protective microenvironments in glioblastoma tumors. We have recently found that GSC niches are hypoxic periarteriolar, whereas in most studies, GSC niches are identified as hypoxic perivascular. The aim of this review is to critically evaluate the literature on perivascular GSC niches to establish whether these are periarteriolar, pericapillary, perivenular, and/or perilymphatic...
January 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29326121/modeling-multiple-myeloma-bone-marrow-interactions-and-response-to-drugs-in-a-3d-surrogate-microenvironment
#5
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/29323706/the-origins-and-homeostasis-of-monocytes-and-tissue-resident-macrophages-in-physiological-situation
#6
REVIEW
Yang Zhao, Weilong Zou, Junfeng Du, Yong Zhao
Monocytes and macrophages are critical effectors and regulators of innate immune response. They not only play crucial and distinctive roles in homeostasis, but also contribute to some pathologic processes. The heterogeneity of the macrophage lineage has been widely recognized and, in part, is a result of the specialization of resident macrophages in particular tissue microenvironments. Monocytes are usually known to originate in the bone marrow from a common myeloid progenitor that is shared with neutrophils, and they are then released into the peripheral blood...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29322846/pi3k-akt-mtor-pathway-in-multiple-myeloma-from-basic-biology-to-clinical-promise
#7
Vijay Ramakrishnan, Shaji Kumar
Multiple myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most common hematological malignancy. The disease is characterized by the accumulation of abnormal plasma cells in the bone marrow that remains in close association with other cells in the marrow microenvironment. In addition to the genomic alterations that commonly occur in MM, the interaction with cells in the marrow microenvironment promotes signaling events within the myeloma cells that enhances survival of MM cells...
January 11, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29314819/modulating-phagocytic-cell-sequestration-by-tailoring-nanoconstruct-softness
#8
Roberto Palomba, Anna Lisa Palange, Ilaria Francesca Rizzuti, Miguel Ferreira, Antonio Cervadoro, Maria Grazia Barbato, Claudio Canale, Paolo Decuzzi
The effect of nanoparticle size, shape and surface properties on cellular uptake has been extensively investigated for its basic science and translational implications. Recently, softness is emerging as a design parameter for modulating the interaction of nanoparticles with cells and the biological microenvironment. Here, circular, quadrangular and elliptical polymeric nanoconstructs of different sizes are realized with a Young's modulus ranging from ∽ 100 kPa (soft) to 10 MPa (rigid). The interaction of these nanoconstructs with professional phagocytic cells is assessed via confocal microscopy and flow cytometry analyses...
January 9, 2018: ACS Nano
https://www.readbyqxmd.com/read/29312584/recipient-bone-marrow-assimilates-the-myeloid-lymphoid-reconstitution-of-distinct-fetal-hematopoietic-stem-cells
#9
Xiao-Lin Guo, Lei Chu, Fang Ke, Li-Li Mu, Zhen Li, Jie-Jing Cai, Huai-Fang Li, Deng-Li Hong
The fetal liver (FL) is a source of hematopoietic stem and progenitor cells (HSPCs) for transplantation. However, whether FL-HSPCs collected at distinct developmental stages reconstitute similarly or differently in the recipient bone marrow (BM) remains undetermined. We examined this problem in a congeneic mouse transplantation model. We first analyzed the lineage components of FL from 12.5 days post-fertilization (dpf) to 18.5 dpf. The myeloid and lymphoid cells were dynamic in absolute number and ratio. The largest difference was between 12...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311715/the-bone-marrow-niche-in-mds-and-mgus-implications-for-aml-and-mm
#10
REVIEW
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29311669/adipocyte-activated-oxidative-and-er-stress-pathways-promote-tumor-survival-in-bone-via-upregulation-of-heme-oxygenase-1-and-survivin
#11
Mackenzie K Herroon, Erandi Rajagurubandara, Jonathan D Diedrich, Elisabeth I Heath, Izabela Podgorski
Metastatic tumor cells engage the local tumor microenvironment and activate specific pro-survival mechanisms to thrive and progress in the harsh bone marrow niche. Here we show that the major contributors to the survival of carcinoma cells that have colonized the bone marrow are the adipocyte-induced oxidative stress and ER stress pathways. We demonstrate that upon exposure to adipocyte-rich environments in vitro or in vivo, bone-trophic prostate and breast tumor cells upregulate the oxidative stress enzyme, HO-1...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29307118/chemotherapy-induced-metastasis-mechanisms-and-translational-opportunities
#12
George S Karagiannis, John S Condeelis, Maja H Oktay
Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a wide range of hematopoietic, mesenchymal and immune progenitor cells, originating from the bone marrow. The actual purpose of these cells is to orchestrate the repair response to the cytotoxic damage of chemotherapy...
January 6, 2018: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/29306107/leukemia-cells-impair-normal-hematopoiesis-and-induce-functionally-loss-of-hematopoietic-stem-cells-through-immune-cells-and-inflammation
#13
Ping Cui, Yuhua Zhang, Maoxiang Cui, Zhihong Li, Guang Ma, Rufeng Wang, Ning Wang, Shujuan Huang, Jie Gao
Bone marrow (BM) failure is often seen in leukemia patients, indicating an abnormal hematopoietic process. However, hematopoiesis in leukemic milieus is largely unknown. In the present study, we utilized one of the most frequent leukemogenic translocations MLL-AF9 to induce leukemia and investigated the hematopoiesis and the activity of hematopoietic stem and progenitor cells (HSPCs) in a leukemic milieu. We found that the phenotypes of the non-leukemic population in leukemic BM were drastically different than normal BM, including blockage of differentiation and a drastically reduced Lin-/Sca+/c-kit+ (LSK) population that contains all HSPCs in leukemic BM...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29305863/mir-449-overexpression-inhibits-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-via-suppressing-sirt1-fra-1-pathway-in-high-glucose-and-free-fatty-acids-microenvironment
#14
Bo Qu, Kai Gong, Hong-Sheng Yang, Yu-Gang Li, Tao Jiang, Zhi-Mou Zeng, Zong-Rui Cao, Xian-Ming Pan
Diabetic osteoporosis is a chronic complication caused by diabetes mellitus, and However, the exact mechanism of diabetes mellitus-induced osteoporosis is still unknown. In this study, we investigate the effect of miR-449 on osteogenic differentiation and its underlying mechanism in human bone marrow-derived mesenchymal stem cells (hBMSCs) with high glucose (HG) and free fatty acids (FFA) treatment. Results showed that after culturing for 14 days, high glucose (HG) and free fatty acids (FFA) treatment dramatically decreased mineralization of human bone marrow-derived mesenchymal stem cells (hBMSCs) compared with cells treated with osteogenic medium (OM) alone...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29304342/chewing-through-roots-how-leukemia-invades-and-disrupts-the-bone-marrow-microenvironment
#15
Owen J Tamplin
The bone marrow (BM) niche is a complex microenvironment that supports healthy hematopoietic stem cells (HSCs) throughout life. In this issue of Cell Stem Cell, Duarte et al. (2018) reveal the spatio-temporal progress of leukemic cells as they invade and occupy the niche, ultimately outcompeting native HSCs.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29299123/inhibition-of-sdf-1-induced-migration-of-oncogene-driven-myeloid-leukemia-by-the-l-rna-aptamer-spiegelmer-nox-a12-and-potentiation-of-tyrosine-kinase-inhibition
#16
Ellen L Weisberg, Martin Sattler, Abdel Kareem Azab, Dirk Eulberg, Anna Kruschinski, Paul W Manley, Richard Stone, James D Griffin
Resistance to targeted tyrosine kinase inhibitors (TKI) remains a challenge for the treatment of myeloid leukemias. Following treatment with TKIs, the bone marrow microenvironment has been found to harbor a small pool of surviving leukemic CD34+ progenitor cells. The long-term survival of these leukemic cells has been attributed, at least in part, to the protective effects of bone marrow stroma. We found that the NOX-A12 'Spiegelmer', an L-enantiomeric RNA oligonucleotide that inhibits SDF-1α, showed in vitro and in vivo activity against BCR-ABL- and FLT3-ITD-dependent leukemia cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296832/a-unique-microenvironment-in-the-developing-liver-supports-the-expansion-of-megakaryocyte-progenitors
#17
Nathalie Brouard, Camille Jost, Nadine Matthias, Camille Albrecht, Sébastien Egard, Poojabahen Gandhi, Catherine Strassel, Tomoko Inoue, Daisuke Sugiyama, Paul J Simmons, Christian Gachet, Francois Lanza
The fetal liver is the site of a major expansion of the hematopoietic stem cell (HSC) pool and is also a privileged organ to study megakaryocyte progenitor differentiation. We identified in the mouse fetal liver at day 13.5 a discrete stromal cell population harboring a CD45-TER119-CD31-CD51+VCAM-1+PDGFRα- (V+P-) phenotype that lacked colony-forming unit fibroblast activity and harbored an hepatocyte progenitor signature. This previously undescribed V+P- population efficiently supported megakaryocyte production from mouse bone marrow HSC and human peripheral blood HSC-myeloid progenitors cultured in the presence of limited cytokine concentrations...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296780/interleukin-6-levels-predict-event-free-survival-in-pediatric-aml-and-suggest-a-mechanism-of-chemotherapy-resistance
#18
Alexandra M Stevens, Jennifer M Miller, Jaime O Munoz, Amos S Gaikwad, Michele S Redell
The tumor microenvironment can protect cancer cells from conventional anticancer therapies. Thus, targeting these protective mechanisms could eradicate therapy-resistant cancer cells and improve outcomes. Interleukin-6 (IL-6) provides extrinsic protection for several solid tumors and multiple myeloma. In pediatric acute myeloid leukemia (AML), IL-6-induced STAT3 signaling frequently becomes stronger at relapse, and increases in IL-6-induced STAT3 activity are associated with inferior survival after relapse...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296749/high-cd123-levels-enhance-proliferation-in-response-to-il-3-but-reduce-chemotaxis-by-downregulating-cxcr4-expression
#19
Nicole L Wittwer, Gabriela Brumatti, Ceilidh Marchant, Jarrod J Sandow, Melanie K Pudney, Mara Dottore, Richard J D'Andrea, Angel F Lopez, Paul G Ekert, Hayley S Ramshaw
High expression of the α chain of the interleukin-3 receptor (IL-3Rα; CD123) is a hallmark of acute myeloid leukemia (AML) leukemic stem cells (LSCs). Elevated CD123 expression is part of the diagnostic immunophenotyping of myeloid leukemia, and higher expression is associated with poor prognosis. However, the biological basis of the poorer prognosis is unclear, and may include heightened IL-3 signaling and non-cell autonomous interactions with the bone marrow (BM) microenvironment. We used TF-1 cells expressing different levels of CD123 and found elevated CD123 levels amplified the proliferative response to exogenous IL-3 and maintained viability in reducing IL-3 concentrations...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288431/thymus-colonization-who-how-how-many
#20
REVIEW
Andreas Krueger
De novo generation of T cells depends on continual colonization of the thymus by bone marrow-derived progenitors. Thymus seeding progenitors (TSPs) constitute a heterogeneous population comprising multipotent and lineage-restricted cell types. Entry into the thymic microenvironment is tightly controlled and recent quantitative studies have revealed that the adult murine thymus only contains approximately 160 niches to accommodate TSPs. Of these niches only about 6% are open for seeding on average at steady-state...
December 29, 2017: Archivum Immunologiae et Therapiae Experimentalis
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