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Bone microenvironment

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https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#1
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29348856/prognostic-value-of-diametrically-polarized-tumor-associated-macrophages-in-multiple-myeloma
#2
Xinyi Chen, Jin Chen, Wenyan Zhang, Ruixue Sun, Ting Liu, Yuhuan Zheng, Yu Wu
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340117/the-regulation-of-pre-metastatic-niche-formation-by-neutrophils
#3
REVIEW
Jadwiga Jablonska, Stephan Lang, Ronit Vogt Sionov, Zvi Granot
Metastasis is a multistep process requiring tumor cell detachment from the primary tumor and migration to target organs through the lymphatic or blood circulatory systems. Specific organs are predisposed to metastases in certain cancers and the formation of supportive metastatic microenvironment determines tumor cell homing. Such an environment is provided by a pre-metastatic niche that is formed through the recruitment of bone marrow-derived myeloid cells, however the mechanisms of its formation are not fully understood...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339479/hif-signaling-in-osteoblast-lineage-cells-promotes-systemic-breast-cancer-growth-and-metastasis-in-mice
#4
Claire-Sophie Devignes, Yetki Aslan, Audrey Brenot, Audrey Devillers, Koen Schepers, Stéphanie Fabre, Jonathan Chou, Amy-Jo Casbon, Zena Werb, Sylvain Provot
Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29337876/microenvironment-stimuli-hgf-and-hypoxia-differently-affected-mir-125b-and-ets-1-function-with-opposite-effects-on-the-invasiveness-of-bone-metastatic-cells-a-comparison-with-breast-carcinoma-cells
#5
Emanuela Matteucci, Paola Maroni, Francesco Nicassio, Francesco Ghini, Paola Bendinelli, Maria Alfonsina Desiderio
We examined the influence of microenvironment stimuli on molecular events relevant to the biological functions of 1833-bone metastatic clone and the parental MDA-MB231 cells. (i) In both the cell lines, hepatocyte growth factor (HGF) and the osteoblasts' biological products down regulated nuclear Ets-1-protein level in concomitance with endogenous miR-125b accumulation. In contrast, under hypoxia nuclear Ets-1 was unchanged, notwithstanding the miR-125b increase. (ii) Also, the 1833-cell invasiveness and the expression of Endothelin-1, the target gene of Ets-1/HIF-1, showed opposite patterns under HGF and hypoxia...
January 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29337200/mimicking-the-3d-biology-of-osteochondral-tissue-with-microfluidic-based-solutions-breakthroughs-towards-boosting-drug-testing-and-discovery
#6
REVIEW
Mariana R Carvalho, Rui Luís Reis, Joaquim Miguel Oliveira
The development of tissue-engineering (TE) solutions for osteochondral (OC) regeneration has been slowed by technical hurdles related to the recapitulation of their complex and hierarchical architecture. OC defects refer to damage of both the articular cartilage and the underlying subchondral bone. To repair an OC tissue defect, the complexity of the bone and cartilage must be considered. To help achieve this, microfluidics is converging with TE approaches to provide new treatment possibilities. Microfluidics uses precise micrometer-to-millimeter-scale fluid flows to achieve high-resolution and spatial and/or temporal control of the cell microenvironment, providing powerful tools for cell culturing...
January 11, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29337106/loss-of-tgf-%C3%AE-signaling-in-osteoblasts-increases-basic-fgf-and-promotes-prostate-cancer-bone-metastasis
#7
Xiangqi Meng, Alexandra Vander Ark, Paul Daft, Erica Woodford, Jie Wang, Zachary Madaj, Xiaohong Li
TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2Col1CreERT KO) or in osteoclasts (Tgfbr2LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2Col1CreERT KO mice, but was inhibited in the Tgfbr2LysMCre KO mice, relative to their respective control Tgfbr2FloxE2 littermates...
January 11, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29336892/gene-therapy-and-gene-editing-strategies-for-hemoglobinopathies
#8
REVIEW
Maria Rosa Lidonnici, Giuliana Ferrari
Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with an integrating lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Studies and safety works demonstrated the potential therapeutic efficacy and safety of this approach, providing the rationale for clinical translation. The outcomes of early clinical trials, although showing promising results, have highlighted the current limitations to a more general application...
January 3, 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29333689/2d-black-phosphorus-reinforced-3d-printed-scaffolds-a-stepwise-countermeasure-for-osteosarcoma
#9
Bowen Yang, Junhui Yin, Yu Chen, Shanshan Pan, Heliang Yao, Youshui Gao, Jianlin Shi
With the ever-deeper understanding of nano-bio interactions and the development of fabrication methodologies of nanomaterials, various therapeutic platforms based on nanomaterials have been developed for next-generation oncological applications, such as osteosarcoma therapy. In this work, a black phosphorus (BP) reinforced 3D-printed scaffold is designed and prepared to provide a feasible countermeasure for the efficient localized treatment of osteosarcoma. The in situ phosphorus-driven, calcium-extracted biomineralization of the intra-scaffold BP nanosheets enables both photothermal ablation of osteosarcoma and the subsequent material-guided bone regeneration in physiological microenvironment, and in the meantime endows the scaffolds with unique physicochemical properties favoring the whole stepwise therapeutic process...
January 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29332538/role-of-infiltrating-monocytes-in-the-development-of-radiation-induced-pulmonary-fibrosis
#10
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/29332359/novel-molecular-and-metabolic-aspects-in-osteosarcoma
#11
Evangelos Tsiambas, Panagiotis P Fotiades, Chrissa Sioka, Dimitrios Kotrotsios, Evangelia Gkika, Andreas Fotopoulos, Stylianos N Mastronikolis, Ilianna E Armata, Evangelos Giotakis, Vasileios Ragos
Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and adolescents. Concerning its molecular landscape, there is no a direct relationship with a specific gene, but a combination of genetic events. A broad spectrum of activated oncogenes and downregulated suppressor genes has been already explored and considered crucial for its progressive pathogenesis. Mechanisms of gene deregulation include amplifications, point mutations, allelic losses and also epigenetic abnormalities such as aberrant promoter methylation...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332174/a-friend-in-knee-ccn3-may-inhibit-osteoarthritis-progression
#12
Alex Peidl
Osteoarthritis (OA) is a major clinical problem among the ageing population, yet no disease-modifying treatments currently exist. This issue arises, in part, due to the complex processes occurring in the microenvironment of articular cartilage that lead to osteoarthritic changes. Gaining a better understanding of these processes is crucial in developing a viable therapy for OA. A recent report in Journal of Bone Mineral Metabolism by Janune et al. (J Bone Miner Metab 35:582-597, 2016) suggests a novel role for CCN3 in maintaining the differentiated phenotype of articular cartilage...
January 13, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29331301/marrow-adipose-tissue-imaging-in-humans
#13
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
#14
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/29330358/pathogenesis-of-bone-disease-in-multiple-myeloma-from-bench-to-bedside
#15
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/29328867/glioma-stem-cell-niches-in-human-glioblastoma-are-periarteriolar
#16
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
#17
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/29323709/osteosarcoma-derived-extracellular-vesicles-induce-a-tumour-like-phenotype-in-normal-recipient-cells
#18
Enrica Urciuoli, Ezio Giorda, Marco Scarsella, Stefania Petrini, Barbara Peruzzi
Osteosarcoma is the most common primary bone cancer and the most frequent cause of bone cancer-related deaths in children and adolescents. Osteosarcoma cells are able to establish a crosstalk with resident bone cells leading to the formation of a deleterious vicious cycle. We hypothesized that osteosarcoma cells can release, in the bone microenvironment, transforming Extracellular Vesicles (EVs) involved in regulating bone cell proliferation and differentiation, thereby promoting tumour growth. We assessed EV production by three osteosarcoma cell lines with increasing aggressiveness in order to investigate their roles in the communication between osteosarcoma cells and normal recipient cells...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323706/the-origins-and-homeostasis-of-monocytes-and-tissue-resident-macrophages-in-physiological-situation
#19
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
#20
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
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