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https://www.readbyqxmd.com/read/27913654/novel-small-molecule-jp-153-targets-the-src-fak-paxillin-signaling-complex-to-inhibit-vegf-induced-retinal-angiogenesis
#1
Jordan J Toutounchian, Jayaprakash Pagadala, Duane D Miller, Jerome Baudry, Frank Park, Edward Chaum, Charles R Yates
Targeting vascular endothelial growth factor (VEGF) is a common treatment strategy for neovascular eye disease, a major cause of vision loss in diabetic retinopathy and age-related macular degeneration. However, the decline in clinical efficacy over time in many patients suggests that monotherapy of anti-VEGF protein therapeutics may benefit from adjunctive treatments. Our previous work has shown that through decreased activation of the cytoskeletal protein paxillin, growth factor-induced ischemic retinopathy in the murine oxygen-induced retinopathy model could be inhibited...
January 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/27913195/breast-cancer-derived-extracellular-vesicles-stimulate-myofibroblast-differentiation-and-pro-angiogenic-behavior-of-adipose-stem-cells
#2
REVIEW
Young Hye Song, Christine Warncke, Sung Jin Choi, Siyoung Choi, Aaron E Chiou, Lu Ling, Han-Yuan Liu, Susan Daniel, Marc A Antonyak, Richard A Cerione, Claudia Fischbach
Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting...
November 29, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27911104/upregulation-of-t-cell-immunoglobulin-and-mucin-domain-containing-3-tim-3-in-monocytes-macrophages-associates-with-gastric-cancer-progression
#3
Zhenxin Wang, Ni Yin, Zixiang Zhang, Yi Zhang, Guangbo Zhang, Weichang Chen
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is an important immune regulatory molecule in cancer immune system. However, expression and function of Tim-3 in monocytes/macrophages in cancer progression mainly remain unclear. In this study, we analyzed Tim-3 levels in peripheral blood mononuclear cells (PBMCs) from 62 gastric cancer patients and 45 healthy controls using flow cytometry and then associated Tim-3 levels with clinical pathological data from patients. We found Tim-3 level was significantly upregulated in monocytes from gastric cancer patients compared with those from healthy controls, and that upregulated Tim-3 levels associated with depth of tumor invasion and tumor lymph node metastasis and advanced clinical stages of gastric cancer patients...
December 2, 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27909731/hypoxia-drives-the-transition-of-human-dermal-fibroblasts-to-a-myofibroblast-like-phenotype-via-the-tgf-%C3%AE-1-smad3-pathway
#4
Bin Zhao, Hao Guan, Jia-Qi Liu, Zhao Zheng, Qin Zhou, Jian Zhang, Lin-Lin Su, Da-Hai Hu
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring...
December 1, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909724/hsp27-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation-through-the-smad3-and-erk-pathways
#5
Gang Wang, Hao Jiao, Jun-Nian Zheng, Xia Sun
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-β (TGF-β)...
November 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27907211/characterization-and-immunomodulatory-effects-of-canine-adipose-tissue-and-bone-marrow-derived-mesenchymal-stromal-cells
#6
Keith A Russell, Natalie H C Chow, David Dukoff, Thomas W G Gibson, Jonathan LaMarre, Dean H Betts, Thomas G Koch
BACKGROUND: Mesenchymal stromal cells (MSC) hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies...
2016: PloS One
https://www.readbyqxmd.com/read/27906099/p311-induces-the-transdifferentiation-of-epidermal-stem-cells-to-myofibroblast-like-cells-by-stimulating-transforming-growth-factor-%C3%AE-1-expression
#7
Haisheng Li, Zhihui Yao, Weifeng He, Hongyan Gao, Yang Bai, Sisi Yang, Lu Zhang, Rixing Zhan, Jianglin Tan, Junyi Zhou, Masao Takata, Jun Wu, Gaoxing Luo
BACKGROUND: Epithelial to mesenchymal transition, especially to myofibroblasts, plays an important role in wound healing, fibrosis, and carcinogenesis. Epidermal stem cells (EpSCs) are responsible for epidermal renewal and wound re-epithelialization. However, it remains unclear whether and how EpSCs transdifferentiate into myofibroblasts or myofibroblast-like cells (MFLCs). Here, we provide the first evidence showing that P311 induces EpSC to MFLC transdifferentiation (EpMyT) via TGFβ1/Smad signaling...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27905881/bone-morphogenetic-protein-2-mediated-pain-and-inflammation-in-a-rat-model-of-posterolateral-arthrodesis
#8
Kendall Mitchell, Jill P Shah, Clifton L Dalgard, Lyubov V Tsytsikova, Ashley C Tipton, Anton E Dmitriev, Aviva J Symes
BACKGROUND: Bone morphogenetic protein-2 (BMP-2) is a pleiotropic, secreted molecule with diverse effects. The potent ability of BMP-2 to stimulate bone growth prompted its widespread clinical use for arthrodesis (spine fusion). However, elevated post-operative pain in patients treated with BMP-2 has been increasingly reported. Determining whether BMP-2 induces pain directly or whether it induces neuroinflammation, which could lower the threshold for pain, is important for developing therapeutic interventions...
December 1, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27905683/prolonged-neutropenia-due-to-antihuman-neutrophil-antigen-2-cd177-antibody-after-bone-marrow-transplantation
#9
Taizo Wada, Satoshi Miyamoto, Hiroyuki Okamoto, Yusuke Matsuda, Tomoko Toma, Kohsuke Imai, Masatoshi Takagi, Tomohiro Morio, Akihiro Yachie
We describe a patient who presented with prolonged neutropenia due to anti-human neutrophil antigen (HNA)-2 (CD177) antibody after allogeneic bone marrow transplantation. A granulocyte immunofluorescence test showed bimodal expression of antineutrophil antibody that resulted from specific binding of anti-HNA-2 to CD177(+) neutrophils from healthy donors. The patient did not respond to granulocyte colony stimulating factor, which is able to upregulate CD177 expression on neutrophils. The low percentage of CD177(+) cells in the few remaining neutrophils supports the possibility of elimination of CD177-upregulated neutrophils...
December 1, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27904683/rapamycin-targets-interleukin-6-il-6-expression-and-suppresses-endothelial-cell-invasion-stimulated-by-tumor-cells
#10
Oleksandr Ekshyyan, Alok R Khandelwal, Xiaohua Rong, Tara Moore-Medlin, Xiaohui Ma, Jonathan Steven Alexander, Cherie-Ann O Nathan
mTOR inhibitors have potent antiangiogenic and anti-lymphangiogenic effects in addition to their growth inhibitory effects in head and neck squamous cell carcinoma (HNSCC). Lymphatogenous spread is much more predominant in HNSCC than hematogenous spread and significantly decreases survival. In this study we evaluated the effects of rapamycin on targeting tumor-stroma crosstalk in HNSCC. HNSCC tumor cells (FaDu) and human lymphatic endothelial cells (HMEC-1A) were co-cultured in various combinations using transwell cell culture inserts to study tumor-stroma crosstalk and the effects of mTOR inhibitor rapamycin...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#11
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27902418/effects-of-the-glucocorticoid-betamethasone-on-the-interaction-of-candida-albicans-with-human-epithelial-cells
#12
Ágnes Jakab, Selene Mogavero, Toni M Förster, Marina Pekmezovic, Nadja Jablonowski, Viktor Dombrádi, István Pócsi, Bernhard Hube
The glucocorticoid betamethasone (BM) is frequently employed in the clinical practice because of its anti-inflammatory and immunosuppressive properties. In this study, we investigated the effect of BM (1 and 2 mM) on the ability of Candida albicans to adhere to, invade and damage oral, intestinal or vaginal epithelial cells, as well as to elicit cytokine and chemokine release. BM at 2 mM concentration stimulated adherence of C. albicans to vaginal cells and facilitated the invasion of intestinal and vaginal epithelia without influencing the growth rate of invading C...
October 20, 2016: Microbiology
https://www.readbyqxmd.com/read/27900635/somatostatin-and-dopamine-receptor-regulation-of-pituitary-somatotroph-adenomas
#13
REVIEW
Anat Ben-Shlomo, Ning-Ai Liu, Shlomo Melmed
Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pasireotide, and to a lesser extent, dopamine and the dopamine analogs bromocriptine and cabergoline, suppress growth hormone (GH) secretion from a GH-secreting pituitary somatotroph adenoma. Somatostatin and dopamine receptors are Gαi-protein coupled that inhibit adenylate cyclase activity and cAMP production and reduce intracellular calcium concentration and calcium flux oscillations...
November 29, 2016: Pituitary
https://www.readbyqxmd.com/read/27900155/normal-platelet-function-in-platelet-concentrates-requires-non-platelet-cells-a-comparative-in-vitro-evaluation-of-leucocyte-rich-type-1a-and-leucocyte-poor-type-3b-platelet-concentrates
#14
William R Parrish, Breana Roides, Julia Hwang, Michael Mafilios, Brooks Story, Samir Bhattacharyya
BACKGROUND: Therapeutic success of platelet-rich plasma (PRP) may vary based on the composition and preparation method. The objective of this study was to evaluate the cellular components of platelet concentrates produced by a leucocyte-rich (LR-PRP) and a leucocyte-poor PRP systems (LP-PRP). METHODS: Parameters evaluated included platelet recovery, platelet concentration, red blood cell (RBC) and white blood cell (WBC) composition, platelet growth factor release and stimulation of human tendon cell proliferation in vitro...
2016: BMJ Open Sport & Exercise Medicine
https://www.readbyqxmd.com/read/27900058/effect-of-surgical-wound-fluids-after-intraoperative-electron-radiotherapy-on-the-cancer-stem-cell-phenotype-in-a-panel-of-human-breast-cancer-cell-lines
#15
Karolina Zaleska, Wiktoria Maria Suchorska, Anna Przybyła, Dawid Murawa
The wound healing process after surgery alters the area surrounding the original tumor and around the scar, and the modified microenvironment is more favorable for tumor recurrence. Intraoperative radiotherapy (IORT) is one of the more novel strategies in breast cancer (BC) treatment. Irradiation during surgery has effects on the tumor microenvironment, abrogating the proliferative cascade induced by surgical wound healing. The aim of the present study was to determine the effect of surgical wound fluids from IOERT treatment (RT-WF) compared with wound fluids from conservative-breast surgery only (WF) on the cancer stem cell phenotype in a panel of BC cell lines...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899381/castration-resistance-in-prostate-cancer-is-mediated-by-the-kinase-nek6
#16
Atish D Choudhury, Anna C Schinzel, Maura B Cotter, Rosina T Lis, Katherine Labella, Ying Jie Lock, Francesca Izzo, Isil Guney, Michaela Bowden, Yvonne Y Li, Jinal Patel, Emily Hartman, Steven A Carr, Monica Schenone, Jacob D Jaffe, Philip W Kantoff, Peter S Hammerman, William C Hahn
In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27898984/transforming-growth-factor-%C3%AE-signaling-cascade-induced-by-mechanical-stimulation-of-fluid-shear-stress-in-cultured-corneal-epithelial-cells
#17
Tsugiaki Utsunomiya, Akihiro Ishibazawa, Taiji Nagaoka, Kazuomi Hanada, Harumasa Yokota, Nobuhito Ishii, Akitoshi Yoshida
Purpose: Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs). Methods: The HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) with the parallel-plate type of flow chamber. Wound healing, cellular proliferation, growth factor expression, TGF-β1 concentration in the culture supernatant, and phosphorylation of SMAD2 were investigated...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27898662/kinase-inhibition-leads-to-hormesis-in-a-dual-phosphorylation-dephosphorylation-cycle
#18
Peter Rashkov, Ian P Barrett, Robert E Beardmore, Claus Bendtsen, Ivana Gudelj
Many antimicrobial and anti-tumour drugs elicit hormetic responses characterised by low-dose stimulation and high-dose inhibition. While this can have profound consequences for human health, with low drug concentrations actually stimulating pathogen or tumour growth, the mechanistic understanding behind such responses is still lacking. We propose a novel, simple but general mechanism that could give rise to hormesis in systems where an inhibitor acts on an enzyme. At its core is one of the basic building blocks in intracellular signalling, the dual phosphorylation-dephosphorylation motif, found in diverse regulatory processes including control of cell proliferation and programmed cell death...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27897101/platelets-from-glioblastoma-patients-promote-angiogenesis-of-tumor-endothelial-cells-and-exhibit-increased-vegf-content-and-release
#19
Clara Di Vito, Stefania Elena Navone, Giovanni Marfia, Loubna Abdel Hadi, Maria Elisa Mancuso, Alessandro Pecci, Francesco Maria Crisà, Valeria Berno, Paolo Rampini, Rolando Campanella, Laura Riboni
Glioblastoma multiforme (GBM) is the most common and fatal intracranial cancer in humans and exhibits intense and aberrant angiogenesis that sustains its malignancy and involves several angiogenic signals. Among them, vascular endothelial growth factor (VEGF) plays a key role and is overexpressed in GBM. Different cells appear to act as triggers of the aberrant angiogenesis, and, among them, platelets act as key participants. In order to provide further insights into the platelet features and angiogenic role in GBM, this study investigated the effects of platelet releasate on GBM-derived endothelial cells (GECs) and the levels of VEGF and endostatin, as pro- and anti-angiogenic components of platelet releasate from GBM patients...
November 29, 2016: Platelets
https://www.readbyqxmd.com/read/27896599/inflammatory-cell-response-to-ultra-thin-amorphous-and-crystalline-hydroxyapatite-surfaces
#20
Louise Rydén, Omar Omar, Anna Johansson, Ryo Jimbo, Anders Palmquist, Peter Thomsen
It has been suggested that surface modification with a thin hydroxyapatite (HA) coating enhances the osseointegration of titanium implants. However, there is insufficient information about the biological processes involved in the HA-induced response. This study aimed to investigate the inflammatory cell response to titanium implants with either amorphous or crystalline thin HA. Human mononuclear cells were cultured on titanium discs with a machined surface or with a thin, 0.1 μm, amorphous or crystalline HA coating...
January 2017: Journal of Materials Science. Materials in Medicine
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