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P Gómez-Contreras, J M Ramiro-Díaz, A Sierra, C Stipp, F E Domann, R J Weigel, G Lal
ECM1 overexpression is an independent predictor of poor prognosis in primary breast carcinomas, however the mechanisms by which ECM1 affects tumor progression have not been completely elucidated. ECM1 was silenced in the triple-negative breast cancer cell lines Hs578T and MDAMB231 using siRNA and the cells were evaluated for changes in morphology, migration, invasion and adhesion. Actin cytoskeleton alterations were evaluated by fluorescent staining and levels of activated Rho GTPases by pull down assays. ECM1 downregulation led to significantly diminished cell migration (p = 0...
October 21, 2016: Clinical & Experimental Metastasis
Shinnosuke Ikemura, Nao Aramaki, Satoshi Fujii, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Takeshi Kuwata, Motohiro Kojima, Atsushi Ochiai, Tomoko Betsuyaku, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases...
October 20, 2016: Cancer Science
Zenei Taira, Yukari Ueda, Hiroshi Monmasu, Daisuke Yamase, Sayaka Miyake, Maya Shiraishi
Two specific signals for regulating liver regeneration were found after 70% partial hepatectomy (PH) in rats. The first finding was a sustained increasing signal of intracellular Ca(2+) ([Ca(2+)]i) in hepatocytes, consisting of two successive peaks with the first narrow peak at 1 hour and the second broad peak increasing by day 3 and then returning to normal by day 4. The second finding was an abnormal peak in the restoring ratio (Rr) curve of liver regeneration after 70% PH at day 4, where the Rr exceeded 100% temporarily, returned to a lower level, and then proceeded to a termination phase of liver regeneration...
2016: Journal of Experimental Pharmacology
Whitney A Greene, Teresa A Burke, Elaine D Por, Ramesh R Kaini, Heuy-Ching Wang
Purpose: The purpose of this study was to characterize the secretion profile of induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. iPS-RPE was used to develop an in vitro wound healing model. We hypothesized that iPS-RPE secretes cytokines and growth factors which act in an autocrine manner to promote migration and proliferation of cells during wound healing. Methods: iPS-RPE was grown in transwells until fully confluent and pigmented...
August 1, 2016: Investigative Ophthalmology & Visual Science
Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde
INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis. METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models. RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract...
October 14, 2016: European Journal of Cancer
Shirin Doroudgar, Pearl Quijada, Mathias Konstandin, Kelli Ilves, Kathleen Broughton, Farid G Khalafalla, Alexandria Casillas, Kristine Nguyen, Natalie Gude, Haruhiro Toko, Luis Ornelas, Donna J Thuerauf, Christopher C Glembotski, Mark A Sussman, Mirko Völkers
BACKGROUND: Myocardial infarction is followed by cardiac dysfunction, cellular death, and ventricular remodeling, including tissue fibrosis. S100A4 protein plays multiple roles in cellular survival, and tissue fibrosis, but the relative role of the S100A4 in the myocardium after myocardial infarction is unknown. This study aims to investigate the role of S100A4 in myocardial remodeling and cardiac function following infarct damage. METHODS AND RESULTS: S100A4 expression is low in the adult myocardium, but significantly increased following myocardial infarction...
October 6, 2016: Journal of Molecular and Cellular Cardiology
Daxiang Chen, Zewei Zheng, Bin Xiao, Wei Li, Mingjian Long, Huiqin Chen, Ming Li, Daniel L Rock, Wenbo Hao, Shuhong Luo
Orf virus (ORFV), a member of Parapoxvirus, has evolved various strategies to modulate the immune responses of host cells. The ORFV-encoded protein ORFV002, a regulator factor, has been found to inhibit the acetylation of NF-κB-p65 by blocking phosphorylation of NF-κB-p65 at Ser(276) and also to disrupt the binding of NF-κB-p65 and p300. To explore the mechanism by which ORFV002 regulates NF-κB signaling, the understanding of ORFV002 potential binding partners in host cells is critical. In this study, ovine S100 calcium binding protein A4 (S100A4), prolyl endopeptidase-like (PREPL) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8) were found to interact with ORFV002 based on the yeast two-hybrid (Y2H) assay using a cDNA library derived from primary ovine fetal turbinate cells (OFTu)...
2016: Frontiers in Microbiology
Li Lei, Li Tang
Schwann cells (SCs) have been reported as a possible source of neurotrophic support for spiral ganglion neurons (SGNs). This study was aimed to investigate whether S100A4 was contributed in the functional effects of SCs on SGNs. SCs were transfected with S100A4 vector or small interfering RNA (siRNA) against S100A4, and the transfection efficiency was verified by quantitative PCR (qPCR) and Western blot. The migration of transfected SCs was determined by Transwell assay, and the expression levels of vascular endothelial growth factor precursor (VEGF) and matrix metallopeptidase 9 (MMP-9) were measured by Western blot...
September 26, 2016: Bioengineered
N Ambartsumian, M Grigorian
Chronic inflammation is acknowledged to be a hallmark of neoplasia - both in cancer initiation and metastasis progression. Here we summarise data suggesting that S100A4 is а trigger of the cascade events that establish an inflammatory milieu and provide a potent flame for primary tumour growth and especially for its metastatic dissemination. The S100A4 protein belongs to the S100 superfamily of small Ca^(2+)-binding proteins. Well established function of S100A4 is associated with induction and promotion of tumour metastasis...
July 2016: Molekuliarnaia Biologiia
Julien Guihaire, Ryo Itagaki, Mandy Stubbendorff, Xiaoqin Hua, Tobias Deuse, Sebastian Ullrich, Elie Fadel, Peter Dorfmüller, Robert C Robbins, Hermann Reichenspurner, Udo Schumacher, Sonja Schrepfer
Bronchiolitis obliterans syndrome (BOS) is a main cause of allograft dysfunction and mortality after lung transplantation (LTx). A better understanding of BOS pathogenesis is needed to overcome this treatment-refractory complication. Orthotopic tracheal transplantation using human bronchus was performed in Brown Norway (BN) and nude (RNU) rats. Allografts were recovered in both strains at Day 7 (BN7 , n = 6; RNU7 , n = 7) or Day 28 (BN28 , n = 6; RNU28 , n = 6). Immune response of the host against the bronchial graft was assessed...
September 10, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Jonathan M Fahey, Joseph V Emmer, Witold Korytowski, Neil Hogg, Albert W Girotti
Gliomas are aggressive brain tumors that are resistant to conventional chemotherapy and radiotherapy. Much of this resistance is attributed to endogenous nitric oxide (NO). Recent studies revealed that 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has advantages over conventional treatments for glioblastoma. In this study, we used an in vitro model to assess whether NO from glioblastoma cells can interfere with ALA-PDT. Human U87 and U251 cells expressed significant basal levels of neuronal NO synthase (nNOS) and its inducible counterpart (iNOS)...
September 8, 2016: Photochemistry and Photobiology
Masahito Naito, Keiju Aokage, Kouichi Saruwatari, Kakeru Hisakane, Tomohiro Miyoshi, Tomoyuki Hishida, Junji Yoshida, Sugano Masato, Motohiro Kojima, Takeshi Kuwata, Satoshi Fujii, Atsushi Ochiai, Yukitoshi Sato, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Invasive lepidic predominant adenocarcinoma (LPA) of the lung is thought to progress in a stepwise fashion from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). The aim of this study was to investigate the microenvironmental changes during the development from AIS to LPA. MATERIALS AND METHODS: Clinicopathological characteristics of AIS (n=51), MIA (n=59), LPA smaller than 3cm (LPA-S, n=113), and LPA larger than 3cm (LPA-L, n=47) were analyzed...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Ching Chang Cho, Ruey-Hwang Chou, Chin Yu
The human S100A4 protein binds calcium, resulting in a change in its conformation to promote the interaction with its target protein. Human epidermal growth factor (EGF) is the target protein of S100A4 and a critical ligand of the receptor EGFR. The EGF/EGFR system promotes cell survival, differentiation, and growth by activating several signaling pathways. Amlexanox is an anti-inflammatory and anti-allergic drug that is used to treat recurrent aphthous ulcers. In the present study, we determined that amlexanox interacts with S100A4 using heteronuclear single quantum correlation titration...
2016: PloS One
Changwei Dou, Zhikui Liu, Meng Xu, Yuli Jia, Yufeng Wang, Qing Li, Wei Yang, Xin Zheng, Kangsheng Tu, Qingguang Liu
miR-187-3p, a novel cancer-related microRNA, was previously reported to play promoting or suppressive roles in different malignancies. However, the expression level, biological function, and underlying mechanisms of miR-187-3p in hepatocellular carcinoma (HCC) remain unknown. This study demonstrated that miR-187-3p was significantly down-regulated in HCC tissues and cell lines, and was associated with advanced TNM stage and metastasis in HCC. Functional studies confirmed that miR-187-3p could inhibit the metastasis of HCC both in vitro and in vivo...
October 28, 2016: Cancer Letters
Anssi Lipponen, Jussi Paananen, Noora Puhakka, Asla Pitkänen
We aimed to define the chronically altered gene expression signature of traumatic brain injury (TBI-sig) to discover novel treatments to reverse pathologic gene expression or reinforce the expression of recovery-related genes. Genome-wide RNA-sequencing was performed at 3 months post-TBI induced by lateral fluid-percussion injury in rats. We found 4964 regulated genes in the perilesional cortex and 1966 in the thalamus (FDR < 0.05). TBI-sig was used for a LINCS analysis which identified 11 compounds that showed a strong connectivity with the TBI-sig in neuronal cell lines...
2016: Scientific Reports
Mizuki Kuramochi, Takeshi Izawa, Munmun Pervin, Alexandra Bondoc, Mitsuru Kuwamura, Jyoji Yamate
Drug-induced liver injury (DILI) is a common problem in human medicine and it is a major reason to withdraw marketed drugs. However, the mechanism of DILI is still less known. Damage-associated molecular patterns (DAMPs), such as high-mobility group boxes (HMGBs), S100 proteins and heat shock proteins (HSPs), are released from injured or necrotic cells, bind to toll-like receptors (TLRs) and modulate inflammatory reactions. Here we investigated the kinetics of DAMPs, TLRs and MHC class II in a rat model of DILI with thioacetamide (TAA)...
September 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Osamu Watanabe, Takao Tsuji, Ryota Kikuchi, Masayuki Itoh, Hiroyuki Nakamura, Kazutetsu Aoshiba
Recent evidence suggests that epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of airway obstructive diseases, such as chronic obstructive pulmonary disease, asthma and bronchiolitis obliterans syndrome after lung transplantation. However, whether EMT occurs in an experimental model of airway fibrosis is not well known. We explored evidence of EMT in a murine model of airway fibrosis induced by repeated exposure to naphthalene. Mice were administered intraperitoneal injections of naphthalene or corn oil vehicle once weekly for 14 consecutive weeks...
October 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Wilson Petrushnko, Justin S Gundara, Philip R De Reuver, Greg O'Grady, Jaswinder S Samra, Anubhav Mittal
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. METHODS: A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability...
August 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Cheol Keun Park, Woo Hee Jung, Ja Seung Koo
Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted...
August 2016: Breast Cancer Research and Treatment
Saeka Matsuda, Masahito Shoumura, Naoto Osuga, Hidetsugu Tsujigiwa, Keisuke Nakano, Norimasa Okafuji, Takanaga Ochiai, Hiromasa Hasegawa, Toshiyuki Kawakami
Perforation of floor of the dental pulp is often encountered during root canal treatment in routine clinical practice of dental caries. If perforation were large, granulation tissue would grow to form periodontal polyp. Granulation tissue consists of proliferating cells however their origin is not clear. It was shown that the cells in granulation tissue are mainly from migration of undifferentiated mesenchymal cells of the bone marrow. Hence, this study utilized GFP bone marrow transplantation mouse model. The floor of the pulp chamber in maxillary first molar was perforated using ½ dental round bur...
2016: International Journal of Medical Sciences
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