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Bharti Garg, Bhuwan Giri, Shrey Modi, Vrishketan Sethi, Iris Castro, Oliver Umland, Yuguang Ban, Shweta Lavania, Rajinder Dawra, Sulagna Banerjee, Selwyn Vickers, Nipun B Merchant, Steven Xi Chen, Eli Gilboa, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
BACKGROUND & AIMS: Immunotherapies are ineffective against pancreatic cancer. We investigated whether the activity of nuclear factor (NF)κB in pancreatic stromal cells contributes to an environment that suppresses anti-tumor immune response. METHODS: Pancreata of C57BL/6 or Rag1-/- mice were given pancreatic injections of a combination of KrasG12D/+; Trp53 R172H/+; Pdx-1cre (KPC) pancreatic cancer cells and pancreatic stellate cells (PSCs) extracted from C57BL/6 (control) or mice with disruption of the gene encoding the NFkB p50 subunit (Nfkb1 or p50-/- mice)...
June 14, 2018: Gastroenterology
Marie Besnier, Stefano Gasparino, Rosa Vono, Elena Sangalli, Amanda Facoetti, Valentina Bollati, Laura Cantone, Germana Zaccagnini, Biagina Maimone, Paola Fuschi, Daniel Da Silva, Michele Schiavulli, Sezin Aday, Massimo Caputo, Paolo Madeddu, Costanza Emanueli, Fabio Martelli, Gaia Spinetti
Therapies based on circulating proangiogenic cells (PACs) have shown promise in ischemic disease models but require further optimization to reach the bedside. Ischemia-associated hypoxia robustly increases microRNA-210 (miR-210) expression in several cell types, including endothelial cells (ECs). In ECs, miR-210 represses EphrinA3 (EFNA3), inducing proangiogenic responses. This study provides new mechanistic evidences for a role of miR-210 in PACs. PACs were obtained from either adult peripheral blood or cord blood...
June 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Amnon Peled, Shiri Klein, Katia Beider, Jan A Burger, Michal Abraham
The chemokine receptor CXCR4 and its ligand stromal cell-derived factor-1 (SDF-1/CXCL12) are important players in the cross-talk among lymphoma, myeloma and leukemia cells and their microenvironments. In hematological malignancies and solid tumors, the overexpression of CXCR4 on the cell surface has been shown to be responsible for disease progression, increasing tumor cell survival and chemoresistance and metastasis to organs with high CXCL12 levels (e.g., lymph nodes and bone marrow (BM)). Furthermore, the overexpression of CXCR4 has been found to have prognostic significance for disease progression in many type of tumors including lymphoma, leukemia, glioma, and prostate, breast, colorectal, renal, and hepatocellular carcinomas...
September 2018: Cytokine
Elizabeth J English, Sarah A Mahn, Adriano Marchese
Signaling activated by binding of the C-X-C motif chemokine ligand CXCL12 to its cognate G protein-coupled receptor (GPCR), chemokine C-X-C motif receptor 4 (CXCR4), is linked to metastatic disease. Yet the mechanisms governing CXCR4 signaling remain poorly understood. Here we show that endocytosis and early endosome antigen 1 (EEA1), which is part of the endosome fusion machinery, are required for CXCL12-mediated AKT Ser/Thr kinase (Akt) signaling selective for certain Akt substrates. Pharmacological inhibition of endocytosis partially attenuated CXCL12-induced phosphorylation of Akt, but not phosphorylation of ERK-1/2...
June 13, 2018: Journal of Biological Chemistry
Yu Zhang, Hongxia Zhang, Siyang Lin, Xudong Chen, Yu Yao, XiaoOu Mao, Bei Shao, Qichuan Zhuge, Kunlin Jin
Stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptors CXCR4 and CXCR7 play important roles in brain repair after ischemic stroke, as SDF-1/ CXCR4/CXCR7 chemokine signaling is critical for recruiting stem cells to sites of ischemic injury. Upregulation of SDF-1/CXCR4/CXCR7 chemokine signaling in the ischemic regions has been well-documented in the animal models of ischemic stroke, but not in human ischemic brain. Here, we found that protein expression of SDF-1 and CXCR7, but not CXCR4, were significantly increased in the cortical peri-infarct regions (penumbra) after ischemic stroke in human, compared with adjacent normal tissues and control subjects...
April 2018: Aging and Disease
S Rizvi, S T Raza, F Mahdi, S P Singh, M Rajput, Q Rahman
Background Type 2 diabetes mellitus (T2DM) is a global major health problem resulting from interaction of environmental and genetic factors, examples of the latter being KCNJ11 (coding for part of the ATP-sensitive potassium channel) and SDF-1β (coding for chemokine CXCL12). Our case-control study was conducted to assess whether recessive, dominant or additive genotype model associations of KCNJ11 (E23K, rs5219) and SDF-1β (G801A, rs1801157) were more strongly linked to type 2 diabetes. Subjects & Methods Genetic polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism...
June 12, 2018: British Journal of Biomedical Science
Malcolm Maden, Jason Orr Brant, Andres Rubiano, Aaron Gabriel W Sandoval, Chelsey Simmons, Robert Mitchell, Henry Collin-Hooper, Jason Jacobson, Saleh Omairi, Ketan Patel
The spiny mouse, Acomys cahirinus, is an adult mammal capable of remarkable feats of scar-free tissue regeneration after damage to several organs including the skin and the heart. Here we investigate the regenerative properties of the skeletal muscle of A. cahirinus tibialis anterior in comparison to the lab mouse, Mus musculus. The A. cahirinus TA showed a similar distribution of myosin heavy chain fibre types and a reduced proportion of oxidative fibres compared to M. musculus. There were differences in the matrix components of the TA with regard to collagen VI and the biomechanical properties...
June 11, 2018: Scientific Reports
Naomi Yoshuantari, Didik Setyo Heriyanto, Susanna Hilda Hutajulu, Johan Kurnianda, Ahmad Ghozali
Background: Colorectal cancer (CRC) is both a global and national burden, being the third most common malignancy in men and the second in women, worldwide. The prognosis of CRC is affected by various factors like the histological grade, angiolymphatic invasion, and distant metastases. Metastasis is an intricate process; one of the possible mechanisms is through the interaction of the chemokines CXCL12 and CXCR4. This study aims to reveal the expression patterns of CXCL12 and CXCR4 in CRC...
2018: Gastroenterology Research and Practice
Arnaud Chalin, Benjamin Lefevre, Christelle Devisme, Charlotte Pronier, Virginie Carrière, Vincent Thibault, Laurence Amiot, Michel Samson
BACKGROUND & AIMS: The chemokines CXCL10 (interferon ϒ-inducible protein 10 [IP-10]), CXCL11 (Human interferon inducible T cell alpha chemokine [I-TAC]), CXCL12 (stromal cell derived factor 1 [SDF-1]), and CXCL14 (breast and kidney-expressed chemokine [BRAK]) are involved in cell recruitment, migration, activation, and homing in liver diseases and have been shown to be upregulated during acute liver injury in animal models. However, their expression in patients with acute liver injury is unknown...
June 4, 2018: Cytokine
Chun Liu, Daniela Lewin Mejia, Benjamin Chiang, Kathryn E Luker, Gary D Luker
Extracellular matrix regulates hallmark features of cancer through biochemical and mechanical signals, although mechanistic understanding of these processes remains limited by lack of models that recreate physiology of tumors. To tissue-engineer models that recapitulate three-dimensional architecture and signaling in tumors, there is a pressing need for new materials permitting flexible control of mechanical and biophysical features. We developed a hybrid hydrogel system composed of collagen and alginate to model tumor environments in breast cancer and other malignancies...
June 4, 2018: Acta Biomaterialia
C Mayer, M Adam, L Walenta, N Schmid, H Heikelä, K Schubert, F Flenkenthaler, K-G Dietrich, S Gruschka, G J Arnold, T Fröhlich, J U Schwarzer, F M Köhn, L Strauss, H Welter, M Poutanen, A Mayerhofer
Contractile smooth muscle-like peritubular cells build the wall of seminiferous tubules in men. They are crucial for sperm transport and complement the functions of Sertoli cells by secreting factors, including glial cell line-derived neurotrophic factor. Previous studies revealed that they also secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which has known roles in spermatogenesis. Peritubular cells express the androgen receptor (AR), which is retained in isolated human testicular peritubular cells...
June 5, 2018: Andrology
T Son Nguyen, Tsvee Lapidot, Wolfram Ruf
The hemostatic system plays pivotal roles in injury repair, innate immunity and adaptation to inflammatory challenges. We here review the evidence that these vascular protective mechanisms have non-traditional roles in hematopoietic stem cell (HSC) maintenance in their physiological bone marrow (BM) niches at steady state and under stress. Expression of coagulation factors and the extrinsic coagulation initiator tissue factor by osteoblasts, tissue resident macrophages and megakaryocytes suggests that endosteal as well as vascular HSC niches are functionally regulated by extravascular coagulation...
June 4, 2018: Blood
Carlotta Raschioni, Giulia Bottai, Andrea Sagona, Valentina Errico, Alberto Testori, Wolfgang Gatzemeier, Fabio Corsi, Corrado Tinterri, Massimo Roncalli, Libero Santarpia, Luca Di Tommaso
Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry...
2018: Disease Markers
Kazuhiro Shima, Keisuke Kimura, Masahiko Ishida, Akiko Kishikawa, Saika Ogawa, Jiawei Qi, Wei-Ren Shen, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Hideki Kitaura
C-X-C motif chemokine 12 (CXCL12) belongs to the family of CXC chemokines. Lipopolysaccharide (LPS) induces inflammation-induced osteoclastogenesis and bone resorption, and in recent years, stimulatory effects of CXCL12 on bone resorption have also been reported. In the present study, we investigated the effects of CXCL12 on LPS-induced osteoclastogenesis and bone resorption. LPS was administered with or without CXCL12 onto mouse calvariae by daily subcutaneous injection. Numbers of osteoclasts and bone resorption were significantly elevated in mice co-administered LPS and CXCL12 compared with mice administered LPS alone...
May 29, 2018: Calcified Tissue International
Jinxing Wang, Lushun Yuan, Xingnian Liu, Gang Wang, Yuan Zhu, Kaiyu Qian, Yu Xiao, Xinghuan Wang
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. The present study was conducted to explore the mechanisms and identify the potential target genes for ccRCC using bioinformatics analysis. The microarray data of GSE15641 were screened on Gene-Cloud of Biotechnology Information (GCBI). A total of 32 ccRCC samples and 23 normal kidney samples were used to identify differentially expressed genes (DEGs) between them. Subsequently, the clustering analysis and functional enrichment analysis of these DEGs were performed, followed by protein-protein interaction (PPI) network, and pathway relation network...
June 2018: Oncology Letters
Ian L McAllister, Sarojini Vijayasekaran, Dan Zhang, Samuel McLenachan, Fred Kuanfu Chen, Dao-Yi Yu
The mechanisms of neuronal degeneration and associated acute alterations in intraretinal cytokine and protein levels remain poorly understood in variable ischaemic retinopathies such as in branch retinal vein occlusion (BRVO). Herein we investigate neuronal damage and alterations in retinal cytokines and proteins in a pig model of acute BRVO. Twelve pigs had a BRVO induced photothrombotically in both eyes. Three pigs (6 eyes) each at 2, 6, 10 and 20 days were sacrificed together with an additional 3 control (6 eyes), enucleated, retinas dissected and processed...
May 24, 2018: Experimental Eye Research
Heyang Liu, Zhuanzhen Li, Miao Deng, Qipeng Liu, Ting Zhang, Wanying Guo, Peng Li, Weiqiang Qiao
BACKGROUND: Several studies have demonstrated that stromal cell derived factor-1 (SDF1, also known as CXCL12) expression is a biomarker for breast cancer treatment; however, its significance of prognosis is inconsistent. This study uses a meta-analysis to explore the prognostic value of CXCL12/SDF1 expression in breast cancer. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to November 25, 2017. Studies investigating the correlation between CXCL12/SDF1 expression and survival in breast carcinoma were included...
May 22, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
S Arena, M Salati, G Sorgentoni, F Barbisan, M Orciani
PURPOSE: The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence. METHODS: MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0...
May 23, 2018: Clinical & Translational Oncology
Tulika Kakati, Hasin A Ahmed, Dhruba K Bhattacharyya, Jugal K Kalita
Developing a cost-effective and robust triclustering algorithm that can identify triclusters of high biological significance in the gene-sample-time (GST) domain is a challenging task. Most existing triclustering algorithms can detect shifting and scaling patterns in isolation, they are not able to handle co-occurring shifting-and-scaling patterns. This paper makes an attempt to address this issue. It introduces a robust triclustering algorithm called THD-Tricluster to identify triclusters over the GST domain...
May 7, 2018: Computational Biology and Chemistry
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
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