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Bone microenvironment

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https://www.readbyqxmd.com/read/28087740/bone-microenvironment-changes-in-latexin-expression-promote-chemoresistance
#1
Mi Zhang, Mary Osisami, Jinlu Dai, Jill M Keller, June Escara-Wilke, Atsushi Mizokami, Evan T Keller
: Although docetaxel (DOX) is the standard of care for advanced prostate cancer (PCa), most patients develop resistance to DOX. Therefore, elucidating the mechanism that underlies resistance to DOX is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 PCa cell line and its DOX-resistant derivative (PC3-TxR) revealed decreased latexin (LXN) expression in the resistant cells. LXN expression was inversely correlated with taxane resistance in a panel of PCa cell lines...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28069877/bone-seeking-matrix-metalloproteinase-2-inhibitors-prevent-bone-metastatic-breast-cancer-growth
#2
Marilena Tauro, Gemma Shay, Samer S Sansil, Antonio Laghezza, Paolo Tortorella, Anthony M Neuger, Hatem Soliman, Conor C Lynch
Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor or host derived MMP-2 contributes to breast cancer growth and does so by processing substrates including type I collagen and transforming growth factorβ (TGFβ) latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28068081/peptide-decorated-nanofibrous-niche-augments-in-vitro-directed-osteogenic-conversion-of-human-pluripotent-stem-cells
#3
Yi Deng, Yuanyi Yang, Shicheng Wei
Realization of clinical potential of human pluripotent stem cells (hPSCs) in bone regenerative medicine requires development of simple and safe biomaterials for expansion of hPSCs followed by directing their lineage commitment to osteoblasts. In the present study, a chemically defined peptide-decorated polycaprolactone (PCL) nanofibrous microenvironment was prepared through electrospinning technology and subsequent conjugation with vitronectin peptide to promote the culture and osteogenic potential of hPSCs in vitro...
January 9, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28067666/versatile-humanized-niche-model-enables-study-of-normal-and-malignant-human-hematopoiesis
#4
Ander Abarrategi, Katie Foster, Ashley Hamilton, Syed A Mian, Diana Passaro, John Gribben, Ghulam Mufti, Dominique Bonnet
The BM niche comprises a tightly controlled microenvironment formed by specific tissue and cells that regulates the behavior of hematopoietic stem cells (HSCs). Here, we have provided a 3D model that is tunable in different BM niche components and useful, both in vitro and in vivo, for studying the maintenance of normal and malignant hematopoiesis. Using scaffolds, we tested the capacity of different stromal cell types to support human HSCs. Scaffolds coated with human mesenchymal stromal cells (hMSCs) proved to be superior in terms of HSC engraftment and long-term maintenance when implanted in vivo...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28064238/myeloid-malignancies-and-the-microenvironment
#5
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/28062564/tgf-%C3%AE-bone-morphogenetic-protein-and-activin-signaling-and-the-tumor-microenvironment
#6
Michael W Pickup, Philip Owens, Harold L Moses
The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor β (TGF-β), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28053317/jawbone-microenvironment-promotes-periodontium-regeneration-by-regulating-the-function-of-periodontal-ligament-stem-cells
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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/28039445/aromatase-inhibitor-induced-bone-loss-increases-the-progression-of-estrogen-receptor-negative-breast-cancer-in-bone-and-exacerbates-muscle-weakness-in-vivo
#13
Laura E Wright, Ahmed A Harhash, Wende M Kozlow, David L Waning, Jenna N Regan, Yun She, Sutha K John, Sreemala Murthy, Maryla Niewolna, Andrew R Marks, Khalid S Mohammad, Theresa A Guise
Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Female athymic nude mice underwent ovariectomy (OVX) or sham surgery and were treated with vehicle or AI (letrozole; Let)...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039266/malignant-astrocytic-tumor-progression-potentiated-by-jak-mediated-recruitment-of-myeloid-cells
#14
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
#15
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
#16
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
#17
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
#18
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/28032372/microrna-210-is-increased-and-it-is-required-for-dedifferentiation-of-osteosarcoma-cell-line
#19
Haixia Zhang, Qing Mai, Juntao Chen
Osteosarcoma (OS) is the most common malignant bone tumor and is prevalent in adolescents. In clinical studies, miR-210 has been reported to be tightly correlated to the poor prognosis of OS. Nevertheless, its roles in OS have not been fully elucidated. In view of the central role played by OS stem cells (OSCs) in the malignant progression of OS, this study investigated the influence of miR-210 on the formation of OSCs. Our previous findings suggested that the microenvironment of bone, abundant TGF-β1 and hypoxia, could induce OS cells to dedifferentiate into OSCs...
December 29, 2016: Cell Biology International
https://www.readbyqxmd.com/read/28031160/myelo-erythroid-commitment-after-burn-injury-is-under-beta-adrenergic-control-via-mafb-regulation
#20
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
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