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Bone marrow microenvironment

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https://www.readbyqxmd.com/read/28064238/myeloid-malignancies-and-the-microenvironment
#1
Claudia Korn, Simón Méndez-Ferrer
Research in the last few years has revealed a sophisticated interaction network between multiple bone marrow (BM) cells that regulate different hematopoietic stem cell (HSC) properties, such as proliferation, differentiation, localization and self-renewal during homeostasis. These mechanisms are essential to keep the physiological HSC numbers in check and interfere with malignant progression. Besides the identification of multiple mutations and chromosomal aberrations driving the progression of myeloid malignancies, alterations in the niche compartment recently gained attention in contributing to disease progression...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28053317/jawbone-microenvironment-promotes-periodontium-regeneration-by-regulating-the-function-of-periodontal-ligament-stem-cells
#2
Bin Zhu, Wenjia Liu, Yihan Liu, Xicong Zhao, Hao Zhang, Zhuojing Luo, Yan Jin
During tooth development, the jawbone interacts with dental germ and provides the development microenvironment. Jawbone-derived mesenchymal stem cells (JBMSCs) maintain this microenvironment for root and periodontium development. However, the effect of the jawbone microenvironment on periodontium tissue regeneration is largely elusive. Our previous study showed that cell aggregates (CAs) of bone marrow mesenchymal stem cells promoted periodontium regeneration on the treated dentin scaffold. Here, we found that JBMSCs enhanced not only the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) but also their adhesion to titanium (Ti) material surface...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052520/ikaros-expression-in-distinct-bone-marrow-cell-populations-as-a-candidate-biomarker-for-outcome-with-lenalidomide-dexamethasone-therapy-in-multiple-myeloma
#3
Arnold Bolomsky, Wolfgang Hübl, Stefano Spada, Ercan Müldür, Karin Schlangen, Daniel Heintel, Alberto Rocci, Adalbert Weißmann, Veronique Fritz, Martin Willheim, Niklas Zojer, Antonio Palumbo, Heinz Ludwig
Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the possibility that cell populations in the bone marrow (BM) microenvironment could serve as biomarkers. We therefore analysed gene expression levels of six IMiD target genes in whole BM samples of 44 myeloma patients treated with lenalidomide-dexamethasone...
January 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28049638/leukemic-blasts-program-bone-marrow-adipocytes-to-generate-a-pro-tumoral-microenvironment
#4
Manar S Shafat, Thomas Oellerich, Sebastian Mohr, Stephen D Robinson, Dylan R Edwards, Christopher R Marlein, Rachel E Piddock, Matthew Fenech, Lyubov Zaitseva, Amina Abdul-Aziz, Jeremy Turner, Johnathan A Watkins, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Despite currently available therapies most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesise that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Since adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukaemia cell interactions to determine if they are essential for the growth and survival of AML...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28044259/bortezomib-interferes-with-adhesion-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-through-sparc-up-regulation-in-human-bone-marrow-mesenchymal-stromal-stem-cells
#5
Masaki Iwasa, Yasuo Miura, Aya Fujishiro, Sumie Fujii, Noriko Sugino, Satoshi Yoshioka, Asumi Yokota, Terutoshi Hishita, Hideyo Hirai, Akira Andoh, Tatsuo Ichinohe, Taira Maekawa
The poor prognosis of adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is attributed to leukemia cells that are protected by the bone marrow (BM) microenvironment. In the present study, we explored the pharmacological targeting of mesenchymal stromal/stem cells in BM (BM-MSCs) to eliminate chemoresistant BCP-ALL cells. Human BCP-ALL cells (NALM-6 cells) that adhered to human BM-MSCs (NALM-6/Ad) were highly resistant to multiple anti-cancer drugs, and exhibited pro-survival characteristics, such as an enhanced Akt/Bcl-2 pathway and increased populations in the G0 and G2/S/M cell cycle stages...
January 2, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28044100/photocrosslinkable-chitosan-hydrogels-functionalized-with-the-rgd-peptide-and-phosphoserine-to-enhance-osteogenesis
#6
Soyon Kim, Zhong-Kai Cui, Jiabing Fan, Armita Fartash, Tara L Aghaloo, Min Lee
Hydrogels derived from naturally occurring polymers are attractive matrix for tissue engineering. Here, we report a biofunctional hydrogel for specific use in bone regeneration by introducing Arg-Gly-Asp (RGD)-containing cell adhesive motifs and phosphorylated serine residues, which are prevalent in native bone extracellular matrix and known to promote osteogenesis by enhancing cell-matrix interactions and hydroxyapatite nucleation, into photopolymerizable methacrylated glycol chitosan (MeGC). Incorporation of phosphoserine into MeGC hydrogels increased the ability of the hydrogels to nucleate mineral on their surfaces...
August 21, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28043150/histone-deacetylase-inhibitors-in-plasma-cell-leukemia-treatment-effect-of-bone-marrow-microenvironment
#7
I Burianova, K Kuzelova, O Mitrovsky, I Spicka, P StOckbauer, M Zackova
In the presented study we analysed the effect of histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on human plasma cell leukemia (PCL) cell line UHKT-944 in the presence of bone marrow microenvironment (BMM). For the analysis, the cells were cultured alone, with bone marrow stromal cells (BMSCs), with extracellular matrix (ECM) components or with interleukin-6, and treated with varied concentrations of SAHA and VPA for 24/48 hours. To study the effect of HDACi, we investigated cell proliferation, apoptosis, cell cycle and changes in selected signalling pathways...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28039266/malignant-astrocytic-tumor-progression-potentiated-by-jak-mediated-recruitment-of-myeloid-cells
#8
Prajwal Rajappa, William S Cobb, Emma Vartanian, Yujie Huang, Laura Daly, Caitlin Hoffman, Jane Zhang, Beiyi Shen, Rachel Yanowitch, Kunal Garg, Babacar Cisse, Sara Haddock, Jason T Huse, David J Pisapia, Timothy A Chan, David Lyden, Jacqueline Bromberg, Jeffrey P Greenfield
PURPOSE: While the tumor microenvironment has been known to play an integral role in tumor progression, the function of non-resident bone marrow-derived cells (BMDCs) remains to be determined in neurological tumors. Here we identified the contribution of BMDC recruitment in mediating malignant transformation from low- to high-grade gliomas. EXPERIMENTAL DESIGN: We analyzed human blood and tumor samples from patients with low- and high-grade gliomas. A spontaneous platelet derived growth factor (PDGF) murine glioma model (RCAS) was utilized to recapitulate human disease progression...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28035684/homeostatic-migration-and-distribution-of-innate-immune-cells-in-primary-and-secondary-lymphoid-organs-with-aging
#9
REVIEW
Janko Nikolich-Žugich, John S Davies
Aging of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of aging involves dissociating the effects of aging on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside, and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of studies, as it has the power to dissociate the age of the cell and the age of the microenvironment in which the cell resides or is migrating into...
December 30, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28035364/cyr61-ccn1-stimulates-proliferation-and-differentiation-of-osteoblasts-in-vitro-and-contributes-to-bone-remodeling-in-vivo-in-myeloma-bone-disease
#10
Hui Liu, Fengping Peng, Zhaoyun Liu, Fengjuan Jiang, Lijuan Li, Shan Gao, Guojin Wang, Jia Song, Erbao Ruan, Zonghong Shao, Rong Fu
Cysteine-rich 61 (CYR61/CCN1), a secreted protein in bone marrow (BM) microenvironment, has diverse effects on many cellular activities such as growth and differentiation. However, the effect of CCN1 on osteoblasts (OBs) in myeloma bone disease remains unclear. In our study, the level of CCN1 in multiple myeloma (MM) patients was detected by ELISA and RT-PCR. The proliferation and differentiation of OBs from MM patients were observed after stimulated by CCN1 in vitro. The myeloma cells transduced with CYR61 gene (RPMI‑8226/CYR61) were injected in a mouse model to evaluate the efficacy of CCN1 in vivo and compare with zoledronic acid...
December 22, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28032600/the-function-of-cancer-shed-gangliosides-in-macrophage-phenotype-involvement-with-angiogenesis
#11
Tae-Wook Chung, Hee-Jung Choi, Mi-Ju Park, Hee-Jin Choi, Syng-Ook Lee, Keuk-Jun Kim, Cheorl-Ho Kim, Changwan Hong, Kyun-Ha Kim, Myungsoo Joo, Ki-Tae Ha
Tumor-derived gangliosides in the tumor microenvironment are involved in the malignant progression of cancer. However, the molecular mechanisms underlying the effects of gangliosides shed from tumors on macrophage phenotype remain unknown. Here, we showed that ganglioside GM1 highly induced the activity and expression of arginase-1 (Arg-1), a major M2 macrophage marker, compared to various gangliosides in bone marrow-derived macrophages (BMDM), peritoneal macrophages and Raw264.7 macrophage cells. We found that GM1 bound to macrophage mannose receptor (MMR/CD206) and common gamma chain (γc)...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032590/predicting-the-impact-of-combined-therapies-on-myeloma-cell-growth-using-a-hybrid-multi-scale-agent-based-model
#12
Zhiwei Ji, Jing Su, Dan Wu, Huiming Peng, Weiling Zhao, Brian Nlong Zhao, Xiaobo Zhou
Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031160/myelo-erythroid-commitment-after-burn-injury-is-under-beta-adrenergic-control-via-mafb-regulation
#13
Shirin Hasan, Nicholas B Johnson, Michael J Mosier, Ravi Shankar, Peggie Conrad, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by beta-adrenergic stimulation leading to anemia. In mouse model of scald burn injury we observed, along with a 3-fold increase in bone marrow LSKs (lin(neg) Sca1(+)cKit(+)), the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs)...
December 28, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28028233/aberrantly-expressed-lgr4-empowers-wnt-signaling-in-multiple-myeloma-by-hijacking-osteoblast-derived-r-spondins
#14
Harmen van Andel, Zemin Ren, Iris Koopmans, Sander P J Joosten, Kinga A Kocemba, Wim de Lau, Marie José Kersten, Alexander M de Bruin, Jeroen E J Guikema, Hans Clevers, Marcel Spaargaren, Steven T Pals
The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also affected by, or even addicted to, signals from the microenvironment. As therapeutic targets, these extrinsic signals may be equally significant as mutated oncogenes. In multiple myeloma (MM), a plasma cell malignancy, most tumors display hallmarks of active Wnt signaling but lack activating Wnt-pathway mutations, suggesting activation by autocrine Wnt ligands and/or paracrine Wnts emanating from the bone marrow (BM) niche...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28027646/protein-nanocage-mediated-fibroblast-activation-protein-targeted-photoimmunotherapy-to-enhance-cytotoxic-t-cell-infiltration-and-tumor-control
#15
Zipeng Zhen, Wei Tang, Mengzhe Wang, Shiyi Zhou, Hui Wang, Zhanhong Wu, Zhonglin Hao, Zibo Li, Lin Liu, Jin Xie
Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity...
January 4, 2017: Nano Letters
https://www.readbyqxmd.com/read/28025941/bone-a-fertile-soil-for-cancer-metastasis
#16
Thomas Coughlin, Ricardo Romero Moreno, Devon Mason, Lukas Nystrom, Joel Boerckel, Glen Niebur, Laurie E Littlepage
Bone is one of the most common and most dangerous sites for metastatic growth across cancer types, and bone metastasis remains incurable. However, the processes by which cancers preferentially metastasize to bone are not well understood. In this review we summarize the morphological features, physical properties, and cell signaling events that make bone a unique site for metastasis and bone remodeling. The signaling crosstalk between the tumor cells and bone cells begins a vicious cycle, which describes the self-sustaining feedback loop between the tumor cells and the bone microenvironment composed of osteoclasts, osteoblasts, other bone marrow cells, bone matrix, and vasculature to support both tumor growth and bone destruction...
December 26, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28024517/-role-of-bone-marrow-mesenchymal-stem-cells-in-resistance-of-chronic-myeloid-leukemia-to-tyrosine-kinase-inhibitors-review
#17
Xiao-Yan Zhang, Qian Wan, Li-Jun Fang, Jian Li
Chronic myeloid leukemia (CML) is a disease originated from malignant hematopoietic stem cell disorder. In CML, mesenchymal stem cells(MSC) have been changed in the bone marrow microenvironment, which can protect the leukemia cells from apoptosis induced by tyrosine kinase inhibitors (TKI) and lead to the resistance to TKI by the secretion of soluble factors, involvement in cell-cell adhesion, and so on. This review mainly focuses on the changes of the bone marrow mesenchymal stem cells in CML, as well as the role and mechanism of MSC in the CML resistance of TKI...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28018362/visualization-of-probiotic-mediated-ca-2-signaling-in-intestinal-epithelial-cells-in-vivo
#18
Takahiro Adachi, Shigeru Kakuta, Yoshiko Aihara, Tomonori Kamiya, Yohei Watanabe, Naomi Osakabe, Naoki Hazato, Atsushi Miyawaki, Soichiro Yoshikawa, Takako Usami, Hajime Karasuyama, Hiromi Kimoto-Nira, Kazuhiro Hirayama, Noriko M Tsuji
Probiotics, such as lactic acid bacteria (LAB) and Bacillus subtilis var. natto, have been shown to modulate immune responses. It is important to understand how probiotic bacteria impact intestinal epithelial cells (IECs), because IECs are the first line of defense at the mucosal surface barrier and their activities substantially affect the gut microenvironment and immunity. However, to date, their precise mechanism remains unknown due to a lack of analytical systems available for live animal models. Recently, we generated a conditional Ca(2+) biosensor Yellow Cameleon (YC3...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28011678/enhanced-targeting-of-cml-stem-and-progenitor-cells-by-inhibition-of-porcupine-acyltransferase-in-combination-with-tki
#19
Puneet Agarwal, Bin Zhang, Yinwei Ho, Amy Cook, Ling Li, Fady M Mikhail, Youzhen Wang, Margaret E McLaughlin, Ravi Bhatia
Tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) has limited efficacy against leukemia stem cells (LSC) responsible for disease propagation, and most CML patients require continued TKI treatment to maintain remission. LSC maintenance is related, at least in part, to signals from the bone marrow microenvironment (BMM). Our previous studies have shown that Wnt signaling from the BMM contributes to preservation of CML LSC following TKI treatment. Secretion of Wnt ligands requires their modification by the O-acyl transferase Porcupine (PORCN)...
December 23, 2016: Blood
https://www.readbyqxmd.com/read/28008146/autologous-reconstitution-of-human-cancer-and-immune-system-in-vivo
#20
Juan Fu, Rupashree Sen, David L Masica, Rachel Karchin, Drew Pardoll, Vonn Walter, D Neil Hayes, Christine H Chung, Young J Kim
Correlative studies from checkpoint inhibitor trials have indicated that better understanding of human leukocytic trafficking into the human tumor microenvironment can expedite the translation of future immune-oncologic agents. In order to directly characterize signaling pathways that can regulate human leukocytic trafficking into the tumor, we have developed a completely autologous xenotransplantation method to reconstitute the human tumor immune microenvironment in vivo. We were able to genetically mark the engrafted CD34+ bone marrow cells as well as the tumor cells, and follow the endogenous leukocytic infiltration into the autologous tumor...
December 19, 2016: Oncotarget
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