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https://www.readbyqxmd.com/read/28817220/klk14-interactions-with-hai-1-and-hai-2-serine-protease-inhibitors-a-molecular-dynamics-and-relative-free-energy-calculations-study
#1
Christian Solís-Calero, Hernandes F Carvalho
Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28815768/micro-vesicles-derived-from-human-wharton-s-jelly-mesenchymal-stromal-cells-mitigate-renal-ischemia-reperfusion-injury-in-rats-after-cardiac-death-renal-transplantation
#2
Xiaoqiang Wu, Tianzhong Yan, Zhiwei Wang, Xuan Wu, Guanghui Cao, Chan Zhang, Xiangyong Tian, Junpeng Wang
OBJECTIVES: The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. METHODS: MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumore necrosis factor (TNF)-α and interleukin (IL)-10 levels in the serum...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28810597/dual-inhibition-of-met-and-src-kinase-activity-as-a-combined-targeting-strategy-for-colon-cancer
#3
Na Song, Xiujuan Qu, Shizhou Liu, Simeng Zhang, Jing Liu, Jinglei Qu, Huachuan Zheng, Yunpeng Liu, Xiaofang Che
Hepatocyte growth factor (HGF)/MET signaling is implicated in the development of colorectal cancer (CRC) and possesses therapeutic value for various types of cancer. However, inhibition of MET alone has been demonstrated to have limited efficacy. The present study examined the combined inhibition of MET and SRC kinase activity in colon cancer cells. Furthermore, the role of the HGF/MET pathway in ligand-dependent and -independent activation was demonstrated. The single inhibition of MET by knockdown small interfering RNA or inhibitor indicated a limited anti-viability effects without inhibiting the basal phosphorylation levels of SRC, protein kinase B (AKT) or extracellular signal-regulated kinase (ERK)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28802255/simultaneous-targeting-of-two-distinct-epitopes-on-met-effectively-inhibits-met-and-hgf-driven-tumor-growth-by-multiple-mechanisms
#4
Michael M Grandal, Serhiy Havrylov, Thomas Tuxen Poulsen, Klaus Koefoed, Anna Dahlman, Gunther R Galler, Paolo Conrotto, Sara Collins, Karsten W Eriksen, Dafna Kaufman, George F Vande Woude, Helle J Jacobsen, Ivan D Horak, Michael Kragh, Johan Lantto, Thomas Bouquin, Morag Park, Mikkel Wandahl Pedersen
Increased MET activity is linked with poor prognosis and outcome in several human cancers currently lacking targeted therapies. Here we report on the characterization of Sym015, an antibody mixture composed of two humanized IgG1 antibodies against non-overlapping epitopes of MET. Sym015 was selected by high-throughput screening searching for antibody mixtures with superior growth inhibitory activity against MET-dependent cell lines. Synergistic inhibitory activity of the antibodies comprising Sym015 was observed in several cancer cell lines harboring amplified MET locus and was confirmed in vivo Sym015 was found to exert its activity via multiple mechanisms...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28783177/autophagy-dependent-generation-of-axin2-cancer-stem-like-cells-promotes-hepatocarcinogenesis-in-liver-cirrhosis
#5
J Li, S B Hu, L Y Wang, X Zhang, X Zhou, B Yang, J H Li, J Xiong, N Liu, Y Li, Y Z Wu, Q C Zheng
Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28782183/pectin-nanocoating-reduces-proinflammatory-fibroblast-response-to-bacteria
#6
A Mieszkowska, J Folkert, T Gaber, K Miksch, K Gurzawska
Implant failures are primarily related to bacterial infections and inflammation. Nanocoating of implant devices with organic molecules is a method used for improving their integration into host tissues and limiting inflammation. Bioengineered plant-derived rhamnogalacturonan-Is (RG-Is) from pectins improve tissue regeneration and exhibit anti-inflammatory properties. Therefore, the aim of this study is to evaluate the in vitro effect of RG-I nanocoating on human gingival primary fibroblast (HGF) activity and proinflammatory response following Porphyromonas gingivalis (P...
August 7, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28780159/pyridine-pyrimidine-amides-that-prevent-hgf-induced-epithelial-scattering-by-two-distinct-mechanisms
#7
Adam Siddiqui-Jain, Jacob P Hoj, J Blade Hargiss, Taylor H Hoj, Carter J Payne, Collin A Ritchie, Steven R Herron, Colette Quinn, Jeffrey T Schuler, Marc D H Hansen
Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in individual cells detaching and assuming a migratory and invasive phenotype. Epithelial scattering recapitulates cancer progression and studies have implicated HGF signaling as a driver of cancer metastasis. Inhibitors of HGF signaling have been proposed to act as anti-cancer agents. We previously screened a small molecule library for compounds that block HGF-induced epithelial scattering. Most hits identified in this screen exhibit anti-mitotic properties...
July 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28774345/determination-of-optimized-oxygen-partial-pressure-to-maximize-the-liver-regenerative-potential-of-the-secretome-obtained-from-adipose-derived-stem-cells
#8
Sang Chul Lee, Kee-Hwan Kim, Ok-Hee Kim, Sang Kuon Lee, Ha-Eun Hong, Seong Su Won, Sang-Jin Jeon, Byung Jo Choi, Wonjun Jeong, Say-June Kim
BACKGROUND: A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO2) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined. METHODS: We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO2 (21%, 10%, 5%, and 1%)...
August 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28766361/annals-express-diagnostic-specificity-and-sensitivity-of-pivkaii-gp3-cstb-scca1-and-hgf-for-diagnosis-of-hepatocellular-carcinoma-in-patients-with-alcoholic-liver-cirrhosis
#9
Adriana Unic, Lovorka Derek, Marko Duvnjak, Leonardo Patrlj, Mislav Rakic, Milan Kujundzic, Vesna Renjic, Nikola Stokovic, Petra Dinjar, Anita Jukic, Ivica Grgurevic
INTRODUCTION: Despite of some new treatment possibilities the improvement in survival rate for hepatocellular carcinoma (HCC) patients is still poor due to late diagnosis. The aim of this study was to investigate diagnostic sensitivity and specificity of Protein induced by vitamin K absence or antagonist-II (PIVKAII), Glypican-3 (GP3), Cystatin B (CSTB), Squamous cell carcinoma antigen 1 (SCCA1) and Hepatocyte growth factor (HGF) as potential tumour markers for HCC in patients with alcoholic liver cirrhosis (ALC) using imaging techniques (MSCT and MRI) as reference standards...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28758209/distinct-projection-targets-define-subpopulations-of-mouse-brainstem-vagal-neurons-that-express-the-autism-associated-met-receptor-tyrosine-kinase
#10
Anna Kamitakahara, Hsiao-Huei Wu, Pat Levitt
Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract...
July 31, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28751869/alterations-of-growth-factors-in-autism-and-attention-deficit-hyperactivity-disorder
#11
Alma Y Galvez-Contreras, Tania Campos-Ordonez, Rocio E Gonzalez-Castaneda, Oscar Gonzalez-Perez
Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28751311/identification-of-a-novel-population-of-highly-cytotoxic-c-met-expressing-cd8-t-lymphocytes
#12
Mahdia Benkhoucha, Nicolas Molnarfi, Gürkan Kaya, Elodie Belnoue, Kristbjörg Bjarnadóttir, Pierre-Yves Dietrich, Paul R Walker, Denis Martinvalet, Madiha Derouazi, Patrice H Lalive
CD8(+) cytotoxic T lymphocytes (CTLs) are critical mediators of anti-tumor immunity, and controlling the mechanisms that govern CTL functions could be crucial for enhancing patient outcome. Previously, we reported that hepatocyte growth factor (HGF) limits effective murine CTL responses via antigen-presenting cells. Here, we show that a fraction of murine effector CTLs expresses the HGF receptor c-Met (c-Met(+) CTLs). Phenotypic and functional analysis of c-Met(+) CTLs reveals that they display enhanced cytolytic capacities compared to their c-Met(-) CTL counterparts...
July 27, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28751152/human-umbilical-cord-blood-derived-mesenchymal-stromal-cells-and-small-intestinal-submucosa-hydrogel-composite-promotes-combined-radiation-wound-healing-of-mice
#13
Changsun Lee, Sehwan Shim, Hyosun Jang, Hyunwook Myung, Janet Lee, Chang-Hwan Bae, Jae Kyung Myung, Min-Jung Kim, Seung Bum Lee, Won-Suk Jang, Sun-Joo Lee, Hwi-Yool Kim, Seung-Sook Lee, Sunhoo Park
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are a promising agent for treating impaired wound healing, and their therapeutic potential may be enhanced by employing extracellular matrix scaffolds as cell culture scaffolds or transplant cell carriers. Here, we evaluated the effect of human umbilical cord blood-derived (hUCB)-MSCs and a porcine small intestinal submucosa (SIS)-derived extracellular matrix scaffold in a combined radiation-wound mouse model of impaired wound healing...
July 24, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28739717/potential-implication-of-paxillin-in-cancer-establishment-within-the-bone-environment
#14
Anna D Sobkowicz, Andrew J Sanders, Malcolm D Mason, Wen G Jiang
BACKGROUND: Bone metastases are a common feature of advanced prostatic malignancies. They are characterised by a unique prevalence of osteoblastic phenotype and a poor prognosis. Paxillin is a 68-kDa signal transduction adaptor and scaffold protein that contains motifs involved in the mediation of protein-protein interactions. The state of paxillin phosphorylation is central to determining a cell's ability to adhere, detach and migrate and hence has been linked to processes such as wound repair and tumour metastasis...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28738343/mir-26a-b-inhibit-tumor-growth-and-angiogenesis-by-targeting-the-hgf-vegf-axis-in-gastric-carcinoma
#15
Yiran Si, Haiyang Zhang, Tao Ning, Ming Bai, Yi Wang, Haiou Yang, Xinyi Wang, Jialu Li, Guoguang Ying, Yi Ba
BACKGROUND/AIMS: Abnormal expression of HGF is found in various cancers and correlates with tumor proliferation, metastasis and angiogenesis. However, the regulatory mechanism of the HGF-VEGF axis remains unclear. METHODS: The expression characteristic of HGF in human gastric cancer tissues was shown by an immunohistochemistry assay, and the expression levels of target protein were detected by Western blot. The relative levels of miR-26a/b and target mRNA were examined by qRT-PCR...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28721121/does-the-injection-of-platelet-rich-plasma-induce-changes-in-the-gene-expression-and-morphology-of-intact-thoroughbred-skeletal-muscle
#16
Kentaro Fukuda, Hirofumi Miyata, Atsutoshi Kuwano, Taisuke Kuroda, Norihisa Tamura, Yasumitsu Kotoyori, Yoshinori Kasashima
Platelet-rich plasma (PRP) therapy is promising for treating skeletal muscle injuries in human athletes by promoting muscle regeneration. It might also be useful for treating muscle injuries in equine athletes. In the present study, muscle regeneration induced by injection of PRP into intact muscle of Thoroughbred was investigated. Autologous PRP and saline were injected twice into intact left and right gluteus medius muscles of seven clinically healthy Thoroughbreds. Muscle samples were collected from the injection sites by needle biopsy at 2 and 7 days after PRP injection...
2017: Journal of Equine Science
https://www.readbyqxmd.com/read/28717879/comparison-of-the-effect-of-activated-or-non-activated-prp-in-various-concentrations-on-osteoblast-and-fibroblast-cell-line-proliferation
#17
Surena Vahabi, Zahra Yadegari, Hossein Mohammad-Rahimi
Platelet-rich plasma (PRP) contains growth factors which positively affect cell proliferation, cell differentiation, chemotaxis and intracellular matrix synthesis. All these processes are involved in wound healing and tissue regeneration; thus, PRP as a source of growth factors can be used in periodontal regenerative therapies. The purpose of the present study was to assess the effect of various concentrations of activated and non-activated PRP on proliferation of osteoblasts and fibroblasts in vitro. PRP was obtained from three healthy volunteers...
July 17, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#18
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28716525/peri-tumor-associated-fibroblasts-promote-intrahepatic-metastasis-of-hepatocellular-carcinoma-by-recruiting-cancer-stem-cells
#19
Jinghua Jiang, Fei Ye, Xue Yang, Chen Zong, Lu Gao, Yang Yang, Qiudong Zhao, Zhipeng Han, Lixin Wei
Fibroblasts have been reported to play an important role in hepatocellular carcinoma (HCC). However, the role of fibroblasts have not been fully understood. Conditioned medium collected from human peri-tumor tissue-derived fibroblasts (CM-pTAFs) showed high metastasis ability than human HCC tissues-derived fibroblasts (CM-TAFs). To determine what component was secreted from fibroblasts, we used Bio-Plex analysis system and compared the factors secreted from CM-pTAFs and CM-TAFs, found a series of up-regulated cytokines in the CM-pTAFs, including IL-6, CCL2, CXCL1, CXCL8, SCGF-β, HGF and VEGF...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28713640/human-adipose-derived-mesenchymal-stem-cells-respond-to-short-term-hypoxia-by-secreting-factors-beneficial-for-human-islets-in-vitro-and-potentiate-antidiabetic-effect-in-vivo
#20
Simen W Schive, Mohammad Reza Mirlashari, Grete Hasvold, Mengyu Wang, Dag Josefsen, Hans Petter Gullestad, Olle Korsgren, Aksel Foss, Gunnar Kvalheim, Hanne Scholz
Adipose-derived mesenchymal stem cells (ASCs) release factors beneficial for islets in vitro and protect against hyperglycemia in rodent models of diabetes. Oxygen tension has been shown to induce metabolic changes and alter ASCs' release of soluble factors. The effects of hypoxia on the antidiabetic properties of ASCs have not been explored. To investigate this, we incubated human ASCs for 48 h in 21% (normoxia) or 1% O2 (hypoxia) and compared viability, cell growth, surface markers, differentiation capability, and soluble factors in the conditioned media (CM)...
2017: Cell Medicine
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