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Bone microenvironment

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https://www.readbyqxmd.com/read/29155217/neutrophil-elastase-in-the-tumor-microenvironment
#1
Irina Lerman, Stephen R Hammes
Myeloid cell production within the bone marrow is accelerated in the setting of cancer, and the numbers of circulating and infiltrating neutrophils and granulocytic myeloid derived suppressor cells (MDSCs) correlate with tumor progression and patient survival. Cancer is therefore able to hijack the normally host-protective immune system and use it to further fuel growth and metastasis. Myeloid cells secrete neutrophil elastase and neutrophil extracellular traps (NETs) in response to cues within the tumor microenvironment, thereby leading to enhanced activity in a variety of cancer types...
November 16, 2017: Steroids
https://www.readbyqxmd.com/read/29152658/hepatic-differentiation-of-mouse-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-using-a-novel-3d-culture-system
#2
Qiong Wu, Jing Tang, Yi Li, Li Li, Yujia Wang, Ji Bao, Hong Bu
The development of novel culture systems that mimic the in vivo microenvironment may be beneficial for inducing the differentiation of stem cells and promoting liver function. In the present study, spheroid cultures and decellularized liver scaffolds (DLSs) were utilized to obtain differentiated hepatocyte‑like cells. Mouse bone marrow (BM)‑derived mesenchymal stem cells (MSCs) self‑aggregated into spheroids under low‑attachment conditions and implanted into the DLSs via a negative pressure suction device...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#3
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152068/age-associated-and-therapy-induced-alterations-in-the-cellular-microenvironment-of-experimental-gliomas
#4
Hannah Schneider, Birthe Lohmann, Hans-Georg Wirsching, Kathy Hasenbach, Elisabeth J Rushing, Karl Frei, Martin Pruschy, Ghazaleh Tabatabai, Michael Weller
The poor prognosis associated with advanced age in patients with glioblastoma remains poorly understood. Glioblastoma in the elderly has been particularly associated with vascular endothelial growth factor (VEGF)-dependent angiogenesis, and early uncontrolled studies suggested that the anti-angiogenic agent bevacizumab (BEV), an antibody to VEGF, might be preferentially active in this patient population. Accordingly, we explored host age-dependent differences in survival and benefit from radiotherapy (RT) or BEV in syngeneic mouse glioma models...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150694/inhibition-of-intimal-hyperplasia-in-murine-aortic-allografts-by-administration-of-a-small-molecule-tlr4-inhibitor-tak-242
#5
Chuangyan Wu, Xiangchao Ding, Cheng Zhou, Ping Ye, Yuan Sun, Jie Wu, Anchen Zhang, Xiaofan Huang, Lingyun Ren, Ke Wang, Peng Deng, Zhang Yue, Jiuling Chen, Sihua Wang, Jiahong Xia
Graft arteriosclerosis (GA) is the leading cause of late cardiac allograft dysfunction. The innate immune system plays a major role in GA, paprticularly Toll-like receptor 4 (TLR4) signaling. Here we characterized the role of TLR4 and its antagonist TAK-242 in a mouse model of GA. BALB/c (H-2d) donor aortas were transplanted into C57BL/6 (H-2b) recipients, and the mice received intraperitoneal injection of 3 or 10 mg/kg of TAK-242 or vehicle every other day for 1, 2, 4, 6, 8 and 12 weeks. With TAK-242 administration, intimal hyperplasia initially appeared at 2 weeks after transplantation, and TAK-242 postponed the progression of neointimal formation in allogeneic aortic grafts...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146005/bone-marrow-adipocytes-in-haematological-malignancies
#6
Ewa Frączak, Mateusz Olbromski, Aleksandra Piotrowska, Natalia Glatzel-Plucińska, Piotr Dzięgiel, Jarosław Dybko, Kazimierz Kuliczkowski, Tomasz Wróbel
Bone marrow adipocytes (BMAs) derived from mesenchymal stem cells (MSC) are an active and significant element of the bone marrow microenvironment. They are involved in metabolic functions, complex interactions with other stromal cells, and in the development and progression of tumours. Currently, there is little data regarding the role of BMAs in haematological malignancies. Due to this, we have attempted to characterise the BMAs in these malignancies in terms of quantity and morphology. Our study included 30 patients aged 22-76 with myelo- (n=17) and lymphoproliferative malignancies (n=13), both with and without bone marrow infiltration...
November 13, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29145866/calcium-containing-scaffolds-induce-bone-regeneration-by-regulating-mesenchymal-stem-cell-differentiation-and-migration
#7
Rubén Aquino-Martínez, Alcira P Angelo, Francesc Ventura Pujol
BACKGROUND: Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca(2+)-containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO4) on MSC migration. In addition, to evaluate the influence of CaSO4 on MSC differentiation and the potential molecular mechanisms involved...
November 16, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29145456/regulation-of-the-bone-marrow-microenvironment-by-g-csf-effects-of-g-csf-on-acute-lymphoblastic-leukaemia
#8
Jordan Basnett, Vicki Xie, Adam Cisterne, Ken Bradstock, Linda Bendall
It has been suggested that disruption of the lymphoid niche by G-CSF may be of therapeutic benefit to patients with acute lymphoblastic leukaemia. We used a xenograft model to determine the effect of G-CSF on ALL progression in a minimal residual disease setting. Consistent with the effects on normal murine B cell progenitors, G-CSF slowed disease in the majority of ALL xenografts tested, suggesting that G-CSF may provide benefits beyond neutrophil recovery for ALL patients. However, two of eight xenografts demonstrated accelerated disease progression...
2017: PloS One
https://www.readbyqxmd.com/read/29143796/angelica-sinensis-polysaccharides-ameliorate-stress-induced-premature-senescence-of-hematopoietic-cell-via-protecting-bone-marrow-stromal-cells-from-oxidative-injuries-caused-by-5-fluorouracil
#9
Hanxianzhi Xiao, Lirong Xiong, Xiaoying Song, Pengwei Jin, Linbo Chen, Xiongbin Chen, Hui Yao, Yaping Wang, Lu Wang
Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143459/the-spatial-patterning-of-rgd-and-bmp-2-mimetic-peptides-at-the-subcellular-scale-modulates-human-mesenchymal-stem-cells-osteogenesis
#10
I Bilem, L Plawinski, P Chevallier, C Ayela, E D Sone, G Laroche, M C Durrieu
Engineering artificial extracellular matrices (ECMs), based on the biomimicry of the spatial distribution of proteins and growth factors within their native microenvironment, is of great importance for understanding mechanisms of bone tissue regeneration. Herein, photolithography is used to decorate glass surfaces with subcellular patterns of RGD and BMP-2 ligands; two mimetic peptides recognized to be involved in stem cells osteogenesis. The biological relevance of well-defined RGD and BMP-2 patterned surfaces is evaluated by investigating the differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts, in the absence of induction media...
November 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29141864/il-1%C3%AE-induces-pathologically-activated-osteoclasts-bearing-extremely-high-levels-of-resorbing-activity-a-possible-pathological-subpopulation-of-osteoclasts-accompanied-by-suppressed-expression-of-kindlin-3-and-talin-1
#11
Takuma Shiratori, Yukari Kyumoto-Nakamura, Akiko Kukita, Norihisa Uehara, Jingqi Zhang, Kinuko Koda, Mako Kamiya, Tamer Badawy, Erika Tomoda, Xianghe Xu, Takayoshi Yamaza, Yasuteru Urano, Kiyoshi Koyano, Toshio Kukita
As osteoclasts have the central roles in normal bone remodeling, it is ideal to regulate only the osteoclasts performing pathological bone destruction without affecting normal osteoclasts. Based on a hypothesis that pathological osteoclasts form under the pathological microenvironment of the bone tissues, we here set up optimum culture conditions to examine the entity of pathologically activated osteoclasts (PAOCs). Through searching various inflammatory cytokines and their combinations, we found the highest resorbing activity of osteoclasts when osteoclasts were formed in the presence of M-CSF, receptor activator of NF-κB ligand, and IL-1β...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29141657/local-estrogen-axis-in-the-human-bone-microenvironment-regulates-estrogen%C3%A2-receptor-positive%C3%A2-breast-cancer-cells
#12
Derek F Amanatullah, John S Tamaresis, Pauline Chu, Michael H Bachmann, Nhat M Hoang, Deborah Collyar, Aaron T Mayer, Robert B West, William J Maloney, Christopher H Contag, Bonnie L King
BACKGROUND: Approximately 70% of all breast cancers express the estrogen receptor, and are regulated by estrogen. While the ovaries are the primary source of estrogen in premenopausal women, most breast cancer is diagnosed following menopause, when systemic levels of this hormone decline. Estrogen production from androgen precursors is catalyzed by the aromatase enzyme. Although aromatase expression and local estrogen production in breast adipose tissue have been implicated in the development of primary breast cancer, the source of estrogen involved in the regulation of estrogen receptor-positive (ER+) metastatic breast cancer progression is less clear...
November 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29138883/hallmarks-of-bone-metastasis
#13
REVIEW
Rachelle W Johnson, Larry J Suva
Breast cancer bone metastasis develops as the result of a series of complex interactions between tumor cells, bone marrow cells, and resident bone cells. The net effect of these interactions are the disruption of normal bone homeostasis, often with significantly increased osteoclast and osteoblast activity, which has provided a rational target for controlling tumor progression, with little or no emphasis on tumor eradication. Indeed, the clinical course of metastatic breast cancer is relatively long, with patients likely to experience sequential skeletal-related events (SREs), often over lengthy periods of time, even up to decades...
November 14, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29138574/cancer-cell-dormancy-mechanisms-and-implications-of-cancer-recurrence-and-metastasis
#14
REVIEW
Xiao-Lei Gao, Mei Zhang, Ya-Ling Tang, Xin-Hua Liang
More recently, disease metastasis and relapse in many cancer patients several years (even some decades) after surgical remission are regarded as tumor dormancy. However, the knowledge of this phenomenon is cripplingly limited. Substantial quantities of reviews have summarized three main potential models that can be put forth to explain such process, including angiogenic dormancy, immunologic dormancy, and cellular dormancy. In this review, newly uncovered mechanisms governing cancer cell dormancy are discussed, with an emphasis on the cross talk between dormant cancer cells and their microenvironments...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29138545/activation-of-notch1-signaling-alleviates-dysfunction-of-bone-marrow-derived-mesenchymal-stem-cells-induced-by-cigarette-smoke-extract
#15
Yi Cheng, Wen Gu, Guorui Zhang, Xiaoming Li, Xuejun Guo
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered attractive therapeutic agents for the treatment of COPD. However, little is known about the impact of Notch on the proliferation, migration, and survival of MSCs in a cigarette smoke (CS) microenvironment. Here, we used CS extract to mimic the CS microenvironment in vitro, with the intention to investigate the effect of Notch in regulating proliferation, migration, and survival of BM-MSCs. Rat bone marrow mesenchymal stem cells were infected with lentivirus vector containing the intracellular domain of Notch1 (N1ICD) and challenged with CS extract...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29137349/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#16
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Zhiqiang Wang, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Teresa McQueen, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137304/monocarboxylate-transporter-1-mct1-a-tool-to-stratify-acute-myeloid-leukemia-aml-patients-and-a-vehicle-to-kill-cancer-cells
#17
Filipa Lopes-Coelho, Carolina Nunes, Sofia Gouveia-Fernandes, Rita Rosas, Fernanda Silva, Paula Gameiro, Tânia Carvalho, Maria Gomes da Silva, José Cabeçadas, Sérgio Dias, Luís G Gonçalves, Jacinta Serpa
Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#18
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136112/local-production-of-tenascin-c-acts-as-a-trigger-for-monocyte-macrophage-recruitment-that-provokes-cardiac-dysfunction
#19
Dounia Abbadi, Fanny Laroumanie, Mathilde Bizou, Joffrey Pozzo, Danièle Daviaud, Christine Delage, Denis Calise, Fréderique Gaits-Iacovoni, Marianne Dutaur, Florence Tortosa, Edith Renaud-Gabardos, Victorine Douin-Echinard, Anne-Catherine Prats, Jerome Roncalli, Angelo Parini, Nathalie Pizzinat
Aims: Tenascin-C (TNC) is an endogenous danger signal molecule strongly associated with inflammatory diseases and with poor outcome in patients with cardiomyopathies. Its function within pathological cardiac tissue during pressure overload remains poorly understood. Methods and results: We showed that TNC accumulates after 1 week of transverse aortic constriction (TAC) in the heart of 12-week-old male mice. By cross bone marrow transplantation experiments, we determined that TNC deposition relied on cardiac cells and not on haematopoietic cells...
November 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29131149/three-dimensional-map-of-nonhematopoietic-bone-and-bone-marrow-cells-and-molecules
#20
Daniel L Coutu, Konstantinos D Kokkaliaris, Leo Kunz, Timm Schroeder
The bone marrow (BM) microenvironment contains many types of cells and molecules with roles in hematopoiesis, osteogenesis, angiogenesis and metabolism. The spatial distribution of the different bone and BM cell types remains elusive, owing to technical challenges associated with bone imaging. To map nonhematopoietic cells and structures in bone and BM, we performed multicolor 3D imaging of osteoblastic, vascular, perivascular, neuronal and marrow stromal cells, and extracellular-matrix proteins in whole mouse femurs...
November 13, 2017: Nature Biotechnology
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