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Olugbenga Awolaran, Susan A Brooks, Verna Lavender
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016...
October 14, 2016: Breast: Official Journal of the European Society of Mastology
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
August 2016: Iranian Journal of Basic Medical Sciences
Eric Lik-Hang Lui, Carl Ka-Leong Ao, Lina Li, Mei-Li Khong, Julian Alexander Tanner
Polyphosphate (polyP) is abundant in bone but its roles in signaling and control of gene expression remain unclear. Here, we investigate the effect of extracellular polyP on proliferation, migration, apoptosis, gene and protein expression in human osteoblast-like SaOS-2 cells. Extracellular polyP promoted SaOS-2 cell proliferation, increased rates of migration, inhibited apoptosis and stimulated the rapid phosphorylation of extracellular-signal-regulated kinase (ERK) directly through basic fibroblast growth factor receptor (bFGFR)...
October 28, 2016: Biochemical and Biophysical Research Communications
Frédérique Larousserie, Laura Bsiri, Valérie Dumaine, Céline Dietrich, Anne Audebourg, Brigitte Radenen-Bussière, Philippe Anract, Marie-Cécile Vacher-Lavenu, Odile Devergne
IL-27 regulates immune responses as well as hematopoiesis and bone remodeling, but its cellular sources in the bone remain unknown. In this study, we investigated whether osteoclasts and osteoblasts-the 2 cell types orchestrating bone homeostasis-could be a source of IL-27 and identified stimuli that induce its expression in vitro. We observed that human monocyte-derived osteoclasts expressed a broader range of TLRs than did human primary osteoblasts and that both cell types exhibited a differential induction of IL-27 expression in response to TLR or cytokine stimulation...
September 27, 2016: Journal of Leukocyte Biology
Hui-Jun Xu, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0...
September 15, 2016: Fish & Shellfish Immunology
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
July 2016: Iranian Journal of Basic Medical Sciences
Qiling He, C Scott Swindle, Chao Wan, Robert J Flynn, Robert A Oster, Dongquan Chen, Fengjie Zhang, Yinglan Shu, Christopher A Klug
Long-term self-renewing hematopoietic stem cell (LT-HSC) homeostasis within the bone marrow (BM) of adult mammals is regulated by complex interactions between LT-HSC and a number of niche-associated cell types including mesenchymal stromal/stem cells (MSC), osteoblasts (OB), macrophage, and neuronal cells in close proximity with the vasculature. Here, we cloned and functionally characterized a murine BM MSC sub-population that was uniformly Nestin(+) Lepr(+) Sca-1(+) CD146(+) and could be stably propagated with high CFU-F re-cloning efficiency...
August 19, 2016: Stem Cells
Xiaojuan Wu, Yang Cao, Hui Xiao, Chenglong Li, Jiayuh Lin
The IL-6/GP130/STAT3 pathway is crucial for tumorigenesis in multiple cancer types, including pancreatic cancer and presents as a viable target for cancer therapy. We reported Bazedoxifene, which is approved as a selective estrogen modulator by FDA, as a novel inhibitor of IL-6/GP130 protein-protein interactions using multiple ligand simultaneous docking and drug repositioning approaches. STAT3 is one of the major downstream effectors of IL-6/GP130. Here, we observed Bazedoxifene inhibited STAT3 phosphorylation and STAT3 DNA binding, induced apoptosis, and suppressed tumor growth in pancreatic cancer cells with persistent IL-6/GP130/STAT3 signaling in vitro and in vivo...
August 17, 2016: Molecular Cancer Therapeutics
M D Pastor, A Nogal, S Molina-Pinelo, A Quintanal-Villalonga, R Meléndez, I Ferrer, B Romero-Romero, M J De Miguel, J L López-Campos, J Corral, R García-Carbonero, A Carnero, L Paz-Ares
INTRODUCTION: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are smoking-related diseases, with the presence of COPD itself increasing the risk of developing lung cancer, probably due to underlying inflammation. LC is typically detected at late stages of the disease and carries a poor prognosis. There is an unmet need for methods to facilitate the early detection of lung cancer in high-risk subjects such as smokers METHODS: The expression of inflammatory proteins in bronchoalveolar lavage samples (BALF) was studied by antibody arrays in a prospective cohort of 60 smokers of more than 30 pack-years divided into four groups (control, LC, COPD, LC & COPD)...
August 11, 2016: Journal of Thoracic Oncology
Natalie A Sims
Bone renews itself and changes shape throughout life to account for the changing needs of the body; this requires co-ordinated activities of bone resorbing cells (osteoclasts), bone forming cells (osteoblasts) and bone's internal cellular network (osteocytes). This review focuses on paracrine signaling by the IL-6 family of cytokines between bone cells, bone marrow, and skeletal muscle in normal physiology and in pathological states where their levels may be locally or systemically elevated. These functions include the support of osteoclast formation by osteoblast lineage cells in response to interleukin 6 (IL-6), interleukin 11 (IL-11), oncostatin M (OSM) and cardiotrophin 1 (CT-1)...
October 2016: International Journal of Biochemistry & Cell Biology
Juliane Lokau, Maria Agthe, Christoph Garbers
The cytokines interleukin-11 (IL-11) and IL-6 are important proteins with well-defined pro- and anti-inflammatory functions. They activate intracellular signaling cascades through a homodimer of the ubiquitously expressed signal-transducing β-receptor glycoprotein 130 (gp130). Specificity is gained through the cell- and tissue-specific expression of the nonsignaling IL-11 and IL-6 α-receptors (IL-11R and IL-6R), which determine the responsiveness of the cell to these two cytokines. IL-6 is a rare example, where its soluble receptor (sIL-6R) has agonistic properties, so that the IL-6/sIL-6R complex is able to activate cells that are usually not responsive to IL-6 alone (trans-signaling)...
2016: Mediators of Inflammation
Zhaoming Zhong, Zedong Hu, Yue Jiang, Ruimei Sun, Xue Chen, Hongying Chu, Musheng Zeng, Chuanzheng Sun
Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities...
July 25, 2016: Oncotarget
Ravand Samaeekia, Valery Adorno-Cruz, Jessica Bockhorn, Ya-Fang Chang, Simo Huang, Aleix Prat, Nahun Ha, Golam Kibria, Dezheng Huo, Hui Zheng, Rachel Dalton, Yuhao Wang, Grigoriy Moskalenko, Huiping Liu
PURPOSE: Effective targeting of cancer stem cells is necessary and important for eradicating cancer and reducing metastasis-related mortality. Understanding of cancer stemness-related signaling pathways at the molecular level will help control cancer and stop metastasis in the clinic. EXPERIMENTAL DESIGN: By analyzing microRNA profiles and functions in cancer development, we aimed to identify regulators of breast tumor stemness and metastasis in human xenograft models in vivo and examined their effects on self-renewal and invasion of breast cancer cells in vitro...
July 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Niloufar Monhasery, Jens Moll, Carly Cuman, Manuel Franke, Larissa Lamertz, Rebecca Nitz, Boris Görg, Dieter Häussinger, Juliane Lokau, Doreen M Floss, Roland Piekorz, Eva Dimitriadis, Christoph Garbers, Jürgen Scheller
Interleukin (IL)-11 signaling is involved in various processes, including epithelial intestinal cell regeneration and embryo implantation. IL-11 signaling is initiated upon binding of IL-11 to IL-11R1 or IL-11R2, two IL-11α-receptor splice variants, and gp130. Here, we show that IL-11 signaling via IL-11R1/2:gp130 complexes occurs on both the apical and basolateral sides of polarized cells, whereas IL-6 signaling via IL-6R:gp130 complexes is restricted to the basolateral side. We show that basolaterally supplied IL-11 is transported and released to the apical extracellular space via transcytosis in an IL-11R1-dependent manner...
July 26, 2016: Cell Reports
Cih-En Huang, Yi-Yang Chen, Jung-Jung Chang, Feng-Che Kuan, Kuan-Der Lee, Chang-Hsien Lu, Jrhau Lung, Chien-Heng Shen, Chih-Cheng Chen
OBJECTIVES: Complex and multiple mechanisms are involved in the etiology of Hepatitis C virus-associated immune thrombocytopenia (HCV-ITP). Many hematopoietic growth factors affect the thrombopoiesis. The aim of this study was to clarify the interaction of the thrombopoietic factors in patients with HCV-ITP. METHODS: We selected 33 patients with HCV-ITP and 17 normal individuals. We compare serum interleukin (IL)-3, IL-6, IL-11, thrombopoietin (Tpo), stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-α (TNFα), and spleen size between these two groups...
July 9, 2016: Hematology (Amsterdam, Netherlands)
Pierre Bigot, Leandro M Colli, Mitchell J Machiela, Lea Jessop, Timothy A Myers, Julie Carrouget, Sarah Wagner, David Roberson, Caroline Eymerit, Daniel Henrion, Stephen J Chanock
Genome-wide association studies have identified multiple renal cell carcinoma (RCC) susceptibility loci. Here, we use regional imputation and bioinformatics analysis of the 12p12.1 locus to identify the single-nucleotide polymorphism (SNP) rs7132434 as a potential functional variant. Luciferase assays demonstrate allele-specific regulatory activity and, together with data from electromobility shift assays, suggest allele-specific differences at rs7132434 for AP-1 transcription factor binding. In an analysis of The Cancer Genome Atlas data, SNPs highly correlated with rs7132434 show allele-specific differences in BHLHE41 expression (trend P value=6...
2016: Nature Communications
Ting Zhang, Bota Cui, Pan Li, Zhi He, Chuyan Long, Lu Wei, Zhaoyuan Peng, Guozhong Ji, Faming Zhang
OBJECTIVE: There were no reports on predicting long-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). This study aimed to detect short-term changes of cytokines and C-reactive protein (CRP) in patients with UC undergoing FMT, and to evaluate the predictive value of CRP and cytokines for the long-term efficacy of FMT. METHODS: Nineteen patients with moderate to severe UC (Mayo score ≥ 6) were treated with single fresh FMT through mid-gut...
2016: PloS One
Yang Yang, Yanyan Sun, Laiyang Cheng, Anna Li, Yanjun Shen, Ligang Jiang, Xiaohui Deng, Lan Chao
GRIM-19 is associated with apoptosis, abnormal proliferation, immune tolerance and malignant transformation, and it also plays an important role in early embryonic development. Although the homologous deletion of GRIM-19 causes embryonic lethality in mice, the precise role of GRIM-19 in embryo implantation has not been elucidated. Here we show that GRIM-19 plays an important role in endometrial receptivity and embryo implantation. Day 1 to Day 6 pregnant mouse uteri were collected. Immunohistochemistry studies revealed the presence of GRIM-19 on the luminal epithelium and glandular epithelium throughout the implantation period in pregnant mice...
June 27, 2016: Reproduction, Fertility, and Development
Eugene A Permyakov, Vladimir N Uversky, Sergei E Permyakov
Cytokine interleukin-11 (IL-11) is a multifunctional protein with diverse roles in the normal cell signaling and in various pathologies. The structure of IL-11 is characterized by a four-helix bundle motif comprising two pairs of antiparallel α-helices arranged in an up-up-down-down configuration. Evaluation of the intrinsic disorder predisposition of human IL-11 by several computational tools clearly shows that this protein is predicted to have functional disordered regions potentially involved in interaction with natural binding partners...
September 2016: Cell Biochemistry and Biophysics
Lucia D'Amico, Dimas Belisario, Giorgia Migliardi, Cristina Grange, Benedetta Bussolati, Patrizia D'Amelio, Timothy Perera, Ettore Dalmasso, Luca Dalle Carbonare, Laura Godio, Paolo Comoglio, Livio Trusolino, Riccardo Ferracini, Ilaria Roato
Cancer stem cells (CSCs) are key players in bone metastasis. In some renal tumors CSCs overexpress the HGF receptor c-MET, speculating that c-MET targeting could lead to bone metastasis inhibition. To address this hypothesis we isolated renal CD105+/CD24-CSCs, expressing c-MET receptor from a primary renal carcinoma. Then, to study their ability to metastasize to bone, we injected renal CSCs in NOD/SCID mice implanted with a human bone and we tested the effect of a c-MET inhibitor (JNJ-38877605) on bone metastasis development...
June 14, 2016: Oncotarget
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