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bone marrow stroma

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https://www.readbyqxmd.com/read/28708600/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#1
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, 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...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697683/metastatic-sclerosing-epithelioid-fibrosarcoma-in-bone-marrow
#2
Rana Asakra, Shane Zaidi, Khin Thway
Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive neoplasm thought to be related to low-grade fibromyxoid sarcoma, which typically occurs in middle-aged adults in the deep soft tissues of the lower extremities and trunk. It comprises nests and cords of relatively uniform epithelioid polygonal cells with clear or eosinophilic cytoplasm in densely sclerotic stroma, and it is typically associated with EWSR1 gene rearrangements, and most commonly EWSR1-CREB3L1 fusions. As primary SEF can arise in bone, and bone is also a common metastatic site for SEF, its recognition at this site is important...
July 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28687621/cancer-associated-fibroblasts-share-characteristics-and-pro-tumorigenic-activity-with-mesenchymal-stromal-cells
#3
Lucia Borriello, Rie Nakata, Michael A Sheard, G Esteban Fernandez, Richard Sposto, Jemily Malvar, Laurence Blavier, Hiroyuki Shimada, Shahab Asgharzadeh, Robert C Seeger, Yves A DeClerck
Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship to MSC is not clear. Here we have isolated from primary human neuroblastoma (NB) tumors a population of αFAP- and FSP-1-expressing CAF that share phenotypic and functional characteristics with bone marrow-derived MSC (BM-MSC). Analysis of human NB tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28684528/wnt-%C3%A3-catenin-activation-by-epigenetically-aberrant-stroma-drives-myelodysplastic-syndrome
#4
Tushar Bhagat, Si Chen, Matthias Bartenstein, Trevor S Barlowe, Dagny von Ahrens, Gaurav S Choudhary, Patrick Tivnan, Elianna Amin, A Mario Marcondes, Mathijs A Sanders, Remco M Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Ioannis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafulla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Cs Yeung, Kira Gritsman, Peter D Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc Hgp Raaijmakers, H J Deeg, Michael G Kharas, Amit Verma
The bone marrow microenvironment influences malignant hematopoiesis but how it promotes leukemogenesis has not been elucidated. Additionally, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands...
July 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28680753/efficacy-of-vaccination-with-tumor-exosome-loaded-dendritic-cells-combined-with-cytotoxic-drug-treatment-in-pancreatic-cancer
#5
Li Xiao, Ulrike Erb, Kun Zhao, Thilo Hackert, Margot Zöller
Pancreatic cancer (PaCa) has a dismal prognosis and adjuvant immunotherapy frequently is of low efficacy due to immunosuppressive features of PaCa and PaCa-stroma. We here explored, whether the efficacy of vaccination with tumor-exosome (TEX)-loaded dendritic cells (DC) can be improved by combining with drugs affecting myeloid-derived suppressor cells (MDSC). Experiments were performed with the UNKC6141 PaCa line. UNKC6141 TEX-loaded DC were weekly intravenously injected, mice additionally receiving Gemcitabine (GEM) and/or ATRA and/or Sunitinib (Sun)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28670693/cxcl12-and-cxcr7-are-relevant-targets-to-reverse-cell-adhesion-mediated-drug-resistance-in-multiple-myeloma
#6
Johannes M Waldschmidt, Anna Simon, Dagmar Wider, Stefan J Müller, Marie Follo, Gabriele Ihorst, Sarah Decker, Joschka Lorenz, Manik Chatterjee, Abdel K Azab, Justus Duyster, Ralph Wäsch, Monika Engelhardt
Cell adhesion-mediated drug resistance (CAM-DR) by the bone marrow (BM) is fundamental to multiple myeloma (MM) propagation and survival. Targeting BM protection to increase the efficacy of current anti-myeloma treatment has not been extensively pursued. To extend the understanding of CAM-DR, we hypothesized that the cytotoxic effects of novel anti-myeloma agents may be abrogated by the presence of BM stroma cells (BMSCs) and restored by addition of the CXCL12 antagonist NOX-A12 or the CXCR4 inhibitor plerixafor...
July 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28666252/melittin-suppresses-tumor-progression-by-regulating-tumor-associated-macrophages-in-a-lewis-lung-carcinoma-mouse-model
#7
Chanju Lee, Sung-Joo S Bae, Hwansoo Joo, Hyunsu Bae
Tumor-associated macrophages (TAM) are a major component of tumor stroma. It has been reported that TAMs have M2-like phenotype and facilitate tumor progression by promoting angiogenesis and immunosuppression. Melittin, a major polypeptide of bee venom, has been widely studied as an anti-cancer drug due to its cytotoxicity to malignant cells. However, very little is known regarding the effect of melittin on immune cells in the tumor microenvironment. This study focuses on the effect of melittin on TAMs in a Lewis lung carcinoma mouse model...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659930/functional-and-homeostatic-impact-of-age-related-changes-in-lymph-node-stroma
#8
REVIEW
Heather L Thompson, Megan J Smithey, Charles D Surh, Janko Nikolich-Žugich
Adults over 65 years of age are more vulnerable to infectious disease and show poor responses to vaccination relative to those under 50. A complex set of age-related changes in the immune system is believed to be largely responsible for these defects. These changes, collectively termed immune senescence, encompass alterations in both the innate and adaptive immune systems, in the microenvironments where immune cells develop or reside, and in soluble factors that guide immune homeostasis and function. While age-related changes in primary lymphoid organs (bone marrow, and, in particular, the thymus, which involutes in the first third of life) have been long appreciated, changes affecting aging secondary lymphoid organs, and, in particular, aging lymph nodes (LNs) have been less well characterized...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28659338/high-throughput-profiling-of-signaling-networks-identifies-mechanism-based-combination-therapy-to-eliminate-microenvironmental-resistance-in-acute-myeloid-leukemia
#9
Zhihong Zeng, Wenbin Liu, Twee Tsao, YiHua Qiu, Yang Zhao, Ismael Samudio, Dos D Sarbassov, Steven M Kornblau, Keith A Baggerly, Hagop M Kantarjian, Marina Konopleva, Michael Andreeff
The bone marrow microenvironment is known to provide a survival advantage to residual acute myeloid leukemia cells, possibly contributing to disease recurrence. The mechanisms by which stroma in the microenvironment regulates leukemia survival remain largely unknown. Using reverse phase-protein array technology, we profiled 53 key protein molecules in 11 signaling pathways in 20 primary acute myeloid leukemia samples and two cell lines, aiming to understand stroma-mediated signaling modulation in response to the targeted agents temsirolimus (MTOR), ABT737 (BCL2/BCL-XL), and Nutlin-3a (MDM2), and to identify the effective combination therapy targeting acute myeloid leukemia in the context of the leukemia microenvironment...
June 28, 2017: Haematologica
https://www.readbyqxmd.com/read/28625845/injury-and-defective-regeneration-of-the-epithelial-basement-membrane-in-corneal-fibrosis-a-paradigm-for-fibrosis-in-other-organs
#10
REVIEW
Steven E Wilson, Gustavo K Marino, Andre A M Torricelli, Carla S Medeiros
Myofibroblast-mediated fibrosis is important in the pathophysiology of diseases in most organs. The cornea, the transparent anterior wall of the eye that functions to focus light on the retina, is commonly affected by fibrosis and provides an optimal model due to its simplicity and accessibility. Severe injuries to the cornea, including infection, surgery, and trauma, may trigger the development of myofibroblasts and fibrosis in the normally transparent connective tissue stroma. Ultrastructural studies have demonstrated that defective epithelial basement membrane (EBM) regeneration after injury underlies the development of myofibroblasts from both bone marrow- and keratocyte-derived precursor cells in the cornea...
June 15, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28624051/persistent-injury-associated-anemia-the-role-of-the-bone-marrow-microenvironment
#11
Jessica K Millar, Kolenkode B Kannan, Tyler J Loftus, Ines G Alamo, Jessica Plazas, Philip A Efron, Alicia M Mohr
BACKGROUND: The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28620145/hepatic-stroma-educated-regulatory-dcs-suppress-cd8-t-cell-proliferation-in-mice
#12
Qian Wang, Hao He, Dongwei Chen, Chao Wang, Yingping Xu, Wengang Song
Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the CD4+ T cell response. The present study assessed whether and how liver DCs suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells to express CD25 and CD69, but inhibited their proliferation...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#13
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28578832/a-biophysical-approach-to-quantify-skeletal-stem-cells-trans-differentiation-as-a-model-for-the-study-of-osteoporosis
#14
L Petecchia, F Viti, F Sbrana, M Vassalli, P Gavazzo
The stroma of human bone marrow contains a population of skeletal stem cells (hBM-MSC) which are common ancestors, among the others, of osteoblasts and adipocytes. It has been proposed that the imbalance between hBM-MSC osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. The possibility to reproduce this mechanism in vitro has been demonstrated, providing a good model to disclose the details of the complex bone-fat generation homeostasis...
May 26, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28575019/clinicopathologic-significance-of-the-cxcl1-cxcr2-axis-in-the-tumor-microenvironment-of-gastric-carcinoma
#15
Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Go Masuda, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira
PURPOSE: It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. METHODS: The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#16
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28491436/primary-bronchial-carcinoma-associated-with-bone-marrow-metastasis-and-paraneoplastic-monoclonal-gammopathy-in-a-cat
#17
Mario Cervone, Stéphanie Beurlet
CASE SUMMARY: Herein we describe an unusual metastatic pattern and paraneoplastic manifestation of a bronchial carcinoma in a cat. An 8 year-old cat presented with a diminished appetite, dysphagia, weight loss, lethargy and coughing. Thoracic radiographs revealed a lung mass. Bronchial carcinoma was diagnosed on the basis of histology and was associated with a lymphoplasmocytic infiltration of the fibrovascular stroma. Biochemistry showed hyperproteinaemia. Serum protein electrophoresis showed a narrow spike in the gamma region...
July 2016: JFMS open reports
https://www.readbyqxmd.com/read/28491279/-mesenchymal-stem-cells-fact-or-fiction-and-implications-in-their-therapeutic-use
#18
REVIEW
Pamela Robey
The concept of a post-natal "mesenchymal stem cell" ("MSC") originated from studies focused on bone marrow stromal cells (BMSCs), which are non-hematopoietic adherent cells, a subset of which are skeletal stem cells (SSCs), able to form cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes based on rigorous clonal and differentiation assays. Subsequently, it was speculated that BMSCs could form other mesodermal derivatives and even cell types from other germ layers. Based on BMSC surface markers, representative of fibroblastic cells, and imprecise differentiation assays, it was further imagined that "MSCs" are ubiquitous and equipotent...
2017: F1000Research
https://www.readbyqxmd.com/read/28477013/self-assembling-nanoparticles-encapsulating-zoledronic-acid-inhibit-mesenchymal-stromal-cells-differentiation-migration-and-secretion-of-proangiogenic-factors-and-their-interactions-with-prostate-cancer-cells
#19
Cinzia Borghese, Naike Casagrande, Eliana Pivetta, Alfonso Colombatti, Mariarosaria Boccellino, Evzen Amler, Nicola Normanno, Michele Caraglia, Giuseppe De Rosa, Donatella Aldinucci
Zoledronic Acid (ZA) rapidly concentrates into the bone and reduces skeletal-related events and pain in bone metastatic prostate cancer (PCa), but exerts only a limited or absent impact as anti-cancer activity. Recently, we developed self-assembling nanoparticles (NPS) encapsulating zoledronic acid (NZ) that allowed a higher intratumor delivery of the drug compared with free zoledronic acid (ZA) in in vivo cancer models of PCa. Increasing evidence suggests that Bone Marrow (BM) Mesenchymal stromal cells (BM-MSCs) are recruited into the stroma of developing tumors where they contribute to progression by enhancing tumor growth and metastasis...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28463768/homoharringtonine-enhances-bortezomib-antimyeloma-activity-in-myeloma-cells-adhesion-to-bone-marrow-stromal-cells-and-in-scid-mouse-xenografts
#20
Ping Chen, Qin Yuan, Hui Yang, Xiaofang Wen, Peidong You, Diyu Hou, Jieqiong Xie, Yu Cheng, Huifang Huang
Despite the great progress in the treatment, multiple myeloma (MM) still remains incurable. Bortezomib (BTZ), a reversible inhibitor of the 26S proteasome, is very effective against MM but unable to eradicate the MM cells in bone marrow niche eventually causing the disease relapse. Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits MM both in vitro and in vivo. This study aimed to investigate whether HHT could potentiate the anti-tumor activity of BTZ in MM cells cocultured with bone marrow stromal cells and in vivo xenograft models...
April 25, 2017: Leukemia Research
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