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https://www.readbyqxmd.com/read/28174730/inhibitors-of-arg-gly-asp-binding-integrins-reduce-development-of-pancreatic-fibrosis-in-mice
#1
Barbara Ulmasov, Brent A Neuschwander-Tetri, Jinping Lai, Vladimir Monastyrskiy, Trisha Bhat, Matthew P Yates, Jonathan Oliva, Michael J Prinsen, Peter G Ruminski, David W Griggs
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by the cytokine transforming growth factor β (TGFB). Integrins of the αv family promote TGFB signaling in mice, probably by interacting with the Arg-Gly-Asp (RGD) sequence of the TGFB latency-associated peptide, which frees TGFB to bind its cellular receptors. However, little is known about the role of integrins in the development of CP. We investigated the effects of small-molecule integrin inhibitors in a mouse model of CP...
July 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28161077/m1-macrophages-are-predominantly-recruited-to-the-major-pelvic-ganglion-of-the-rat-following-cavernous-nerve-injury
#2
Hotaka Matsui, Nikolai A Sopko, Johanna L Hannan, Allison A Reinhardt, Max Kates, Takahiro Yoshida, Xiaopu Liu, Fabio Castiglione, Petter Hedlund, Emmanuel Weyne, Maarten Albersen, Trinity J Bivalacqua
INTRODUCTION: Neurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involves injury to the autonomic cavernous nerves, which arise from the major pelvic ganglion (MPG), and subsequent neuroinflammation, which leads to recruitment of macrophages to the injury site. Currently, two macrophage phenotypes are known: neurotoxic M1 macrophages and neuroprotective M2 macrophages. AIM: To examine whether bilateral cavernous nerve injury (BCNI) in a rat model of erectile dysfunction would increase recruitment of neurotoxic M1 macrophages to the MPG...
February 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28160548/regulation-of-mirna-29c-and-its-downstream-pathways-in-preneoplastic-progression-of-triple-negative-breast-cancer
#3
Anjana Bhardwaj, Harpreet Singh, Kimal Rajapakshe, Kazunoshin Tachibana, Nivetha Ganesan, Yinghong Pan, Preethi H Gunaratne, Cristian Coarfa, Isabelle Bedrosian
Little is understood about the early molecular drivers of triple-negative breast cancer (TNBC), making the identification of women at risk and development of targeted therapy for prevention significant challenges. By sequencing a TNBC cell line-based breast cancer progression model we have found that miRNA-29c is progressively lost during TNBC tumorigenesis. In support of the tumor suppressive role of miRNA 29c, we found that low levels predict poor overall patient survival and, conversely, that ectopic expression of miRNA-29c in preneoplastic cell models inhibits growth...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28120021/matrix-metalloproteinase-14-triggers-an-anti-inflammatory-proteolytic-cascade-in-endotoxemia
#4
Alina Aguirre, Jorge Blázquez-Prieto, Laura Amado-Rodriguez, Inés López-Alonso, Estefanía Batalla-Solís, Adrián González-López, Moisés Sánchez-Pérez, Carlos Mayoral-Garcia, Ana Gutiérrez-Fernández, Guillermo M Albaiceta
: ᅟ: Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 (-/-) mice were challenged with lipopolysaccharide. MMP-14 levels decreased after endotoxemia. Mutant animals showed 100% mortality, compared to 50% in wildtype mice...
January 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28053020/blocking-tumor-educated-msc-paracrine-activity-halts-osteosarcoma-progression
#5
Serena Rubina Baglio, Tonny Lagerweij, Maria Pérez Lanzón, Dung Xuan Ho, Nicolas Léveillé, Sonia A Melo, Anne-Marie Cleton-Jansen, Ekaterina S Jordanova, Laura Roncuzzi, Michelina Greco, Monique A J van Eijndhoven, Giulia Grisendi, Massimo Dominici, Roberta Bonafede, Sinead Lougheed, Tanja D de Gruijl, Nicoletta Zini, Silvia Cervo, Agostino Steffan, Vincenzo Canzonieri, Aare Martson, Katre Maasalu, Sulev Koks, Thomas Wurdinger, Nicola Baldini, Dirk M Pegtel
PURPOSE: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets. EXPERIMENTAL DESIGN: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSCs) on osteosarcoma progression...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#6
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27956229/milk-fat-globule-egf-factor-8-secreted-by-mesenchymal-stem-cells-protects-against-liver-fibrosis-in-mice
#7
Su Yeon An, Yu Jin Jang, Hee-Joung Lim, Jiyou Han, Jaehun Lee, Gyunggyu Lee, Ji Young Park, Seo-Young Park, Ji Hyang Kim, Byung-Rok Do, Chugseong Han, Hee-Kyung Park, Ok-Hee Kim, Myeong Jun Song, Say-June Kim, Jong-Hoon Kim
BACKGROUND & AIMS: Mesenchymal stem cells (MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs (UCMSCs) were differentiated into hepatocyte-like cells (hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadruple time-of-flight mass spectrometry...
December 9, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27879343/serine-threonine-kinase-receptor-associated-protein-regulates-early-follicle-development-in-the-mouse-ovary
#8
Isam B Sharum, Sofia Granados-Aparici, Fiona C Warrander, Felicity P Tournant, Mark A Fenwick
The molecular mechanisms involved in regulating the development of small, gonadotrophin-independent follicles are poorly understood; however, many studies have highlighted an essential role for TGFB ligands. Canonical TGFB signalling is dependent upon intracellular SMAD proteins that regulate transcription. STRAP has been identified in other tissues as an inhibitor of the TGFB-SMAD signalling pathway. Therefore, in this study we aimed to determine the expression and role of STRAP in the context of early follicle development...
February 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27859672/immune-activation-and-regulation-related-patterns-in-stable-hand-transplant-recipients
#9
Dorota Kamińska, Katarzyna Kościelska-Kasprzak, Magdalena Krajewska, Adam Chełmoński, Jerzy Jabłecki, Marcelina Żabińska, Marta Myszka, Mirosław Banasik, Maria Boratyńska, Agnieszka Gomółkiewicz, Piotr Dzięgiel, Marian Klinger
We assessed cell subsets and expression of a set of genes related to the T-cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF-B, and TNF-A genes on a custom-designed low-density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations...
November 9, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27827279/plasma-rich-in-growth-factors-promotes-dermal-fibroblast-proliferation-migration-and-biosynthetic-activity
#10
COMPARATIVE STUDY
E Anitua, A Pino, G Orive
OBJECTIVE: The use of plasma rich in growth factors (PRGF) has gained importance in many medical fields due to its regenerative potential. The aim of this study is to evaluate the effects of PRGF on primary skin fibroblasts assessing cell proliferation, migration and secretion of growth factors. The age of the patients from who PRGF was prepared was also studied to determine whether it influenced the outcomes. METHOD: Human dermal fibroblasts were isolated from three healthy volunteers...
November 2, 2016: Journal of Wound Care
https://www.readbyqxmd.com/read/27815749/co-expression-modules-identified-from-published-immune-signatures-reveal-five-distinct-immune-subtypes-in-breast-cancer
#11
Dominic Amara, Denise M Wolf, Laura van 't Veer, Laura Esserman, Michael Campbell, Christina Yau
PURPOSE: There is a growing body of literature demonstrating that immune-related expression signatures predict breast cancer prognosis and chemo-/targeted-therapy responsiveness. However, it is unclear whether these signatures correlate with each other or represent distinct immune-related signals. METHODS: We evaluated 57 published immune-related expression signatures in four public breast cancer datasets totaling 3295 samples. For each dataset, we used consensus clustering to group signatures together based on their co-expression pattern...
November 4, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27808102/bioinspired-seeding-of-biomaterials-using-three-dimensional-microtissues-induces-chondrogenic-stem-cell-differentiation-and-cartilage-formation-under-growth-factor-free-conditions
#12
J Leijten, L S Moreira Teixeira, J Bolander, W Ji, B Vanspauwen, J Lammertyn, J Schrooten, F P Luyten
Cell laden biomaterials are archetypically seeded with individual cells and steered into the desired behavior using exogenous stimuli to control growth and differentiation. In contrast, direct cell-cell contact is instructive and even essential for natural tissue formation. Namely, microaggregation and condensation of mesenchymal progenitor cells triggers chondrogenesis and thereby drives limb formation. Yet a biomimetic strategy translating this approach into a cell laden biomaterial-based therapy has remained largely unexplored...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27806318/med12-mutations-in-breast-phyllodes-tumors-evidence-of-temporal-tumoral-heterogeneity-and-identification-of-associated-critical-signaling-pathways
#13
Marick Laé, Sophie Gardrat, Sophie Rondeau, Camille Richardot, Martial Caly, Walid Chemlali, Sophie Vacher, Jérôme Couturier, Odette Mariani, Philippe Terrier, Ivan Bièche
Exome sequencing has recently identified highly recurrent MED12 somatic mutations in fibroadenomas (FAs) and phyllodes tumors (PTs). In the present study, based on a large series, we confirmed the presence of MED12 exon 1 and 2 mutations in 49% (41/83) of PTs, 70% (7/10) of FAs and 9.1% (1/11) of fibromatoses. We show that MED12 mutations are associated with benign behavior of phyllodes tumors, as they are detected less frequently in malignant PTs (27.6%) compared to benign (58.3%) and borderline (63.3%) PTs, respectively (p = 0...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27773809/transforming-growth-factor-%C3%AE-superfamily-signaling-in%C3%A2-development-of-colorectal-cancer
#14
REVIEW
Barbara Jung, Jonas J Staudacher, Daniel Beauchamp
Transforming growth factor (TGF)-β cytokines signal via a complex network of pathways to regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types. A high percentage of colorectal tumors contain mutations that disrupt TGF-β family member signaling. We review how TGF-β family member signaling is altered during development of colorectal cancer, models of study, interaction of pathways, and potential therapeutic strategies.
January 2017: Gastroenterology
https://www.readbyqxmd.com/read/27769060/mir-185-akt-and-mir-29a-collagen-1a-pathways-are-activated-in-ipf-bal-cells
#15
Eliza Tsitoura, Athol U Wells, Kostantinos Karagiannis, Ismini Lasithiotaki, Eirini Vasarmidi, Eleni Bibaki, Chara Koutoulaki, Hiroe Sato, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells...
15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27693511/infection-of-hepatocytes-with-hcv-increases-cell-surface-levels-of-heparan-sulfate-proteoglycans-uptake-of-cholesterol-and-lipoprotein-and-virus-entry-by-up-regulating-smad6-and-smad7
#16
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6 and another inhibitory SMAD (SMAD7) promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with Japanese fulminant hepatitis-1 (JFH1) HCV cell culture system (HCVcc)...
January 2017: Gastroenterology
https://www.readbyqxmd.com/read/27683263/smad3-activation-a-converging-point-of-dysregulated-tgf-beta-superfamily-signaling-and-genetic-aberrations-in-granulosa-cell-tumor-development
#17
Xin Fang, Yang Gao, Qinglei Li
Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human. However, our understanding of the role of cell signaling in GCT development is far from complete. Increasing lines of evidence highlight the importance of TGF-beta (TGFB) superfamily signaling in the pathogenesis of GCTs...
November 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27663597/identification-of-keratin19-positive-cancer-stem-cells-associating-human-hepatocellular-carcinoma-using-18f-fluorodeoxyglucose-positron-emission-tomography
#18
Takayuki Kawai, Kentaro Yasuchika, Satoru Seo, Tatsuya Higashi, Takamichi Ishii, Yuya Miyauchi, Hidenobu Kojima, Ryoya Yamaoka, Hokahiro Katayama, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Ken Fukumitsu, Yuji Nakamoto, Etsuro Hatano, Shinji Uemoto
Purpose The current lack of tools for easy assessment of cancer stem cells (CSCs) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker, and that positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is an effective method for predicting postoperative outcome in HCC. Herein, we examined whether K19+ HCC-CSCs can be tracked using 18F-FDG-PET. Experimental Design K19 and glucose transporter-1 (GLUT1) expression was evaluated by immunohistochemistry in 98 HCC patients who underwent 18F-FDG-PET scans before primary tumor resection...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27632054/hypoxia-increased-expression-of-genes-involved-in-inflammation-dedifferentiation-pro-fibrosis-and-extracellular-matrix-remodeling-of-human-bladder-smooth-muscle-cells
#19
Bridget Wiafe, Adetola Adesida, Thomas Churchill, Esther Ekpe Adewuyi, Zack Li, Peter Metcalfe
Partial bladder outlet obstruction (pBOO) is characterized by exaggerated stretch, hydrodynamic pressure, and inflammation which cause significant damage and fibrosis to the bladder wall. Several studies have implicated hypoxia in its pathophysiology. However, the isolated progressive effects of hypoxia on bladder cells are not yet defined. Sub-confluent normal human bladder smooth muscle cells (hbSMC) were cultured in 3% O2 tension for 2, 24, 48, and 72 h. RNA, cellular proteins, and secreted proteins were used for gene expression analysis, immunoblotting, and ELISA, respectively...
September 8, 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27624535/hierarchical-heterogeneity-in-mammary-tumors-and-its-regulation-by-autophagy
#20
Syn Kok Yeo, Jun-Lin Guan
Intra-tumor heterogeneity can be attributed in part to the ability of tumor cells to acquire traits associated with less differentiated cells. In MMTV-PyMT mammary tumors, this hierarchical heterogeneity can be illustrated with the use of ITGB1/CD29(hi) ITGB3/CD61(+) markers to enrich for mammary stem-like cells and ALDH(+) to identify luminal progenitor-like cells. Macroautophagy/autophagy appears to be important for maintaining the cancer stem-like traits of both these populations. Interestingly, the regulation of these distinct cancer stem-like cells by autophagy occurs through EGFR-STAT3 and TGFB/TGF-β-SMAD pathways, respectively...
October 2, 2016: Autophagy
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