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https://www.readbyqxmd.com/read/28445938/pirfenidone-normalizes-the-tumor-microenvironment-to-improve-chemotherapy
#1
Christiana Polydorou, Fotios Mpekris, Panagiotis Papageorgis, Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445805/fak-phosphorylation-plays-a-central-role-in-thrombin-induced-rpe-cell-migration
#2
E D Aguilar-Solis, A M López-Colomé, I Lee-Rivera, A Alvarez-Arce, E López
The migration of retinal pigment epithelial (RPE) cells is an important step in various pathologic conditions including subretinal neovascularization (SRN), proliferative vitreoretinopathy (PVR) and, importantly, as a consequence of retinal surgery. Therefore, the elucidation of the mechanisms underlying RPE trans-differentiation and migration is essential for devising effective treatments aimed to the prevention of these disorders. A common event in these pathologies is the alteration of the blood-retina barrier (BRB), which allows the interaction of RPE cells with thrombin, a pro-inflammatory protease contained in serum...
April 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28445803/jetvalve-rapid-manufacturing-of-biohybrid-scaffolds-for-biomimetic-heart-valve-replacement
#3
Andrew K Capulli, Maximillian Y Emmert, Francesco S Pasqualini, Debora Kehl, Etem Caliskan, Johan U Lind, Sean P Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Weber, Josue A Goss, Simon P Hoerstrup, Kevin Kit Parker
Tissue engineered scaffolds have emerged as a promising solution for heart valve replacement because of their potential for regeneration. However, traditional heart valve tissue engineering has relied on resource-intensive, cell-based manufacturing, which increases cost and hinders clinical translation. To overcome these limitations, in situ tissue engineering approaches aim to develop scaffold materials and manufacturing processes that elicit endogenous tissue remodeling and repair. Yet despite recent advances in synthetic materials manufacturing, there remains a lack of cell-free, automated approaches for rapidly producing biomimetic heart valve scaffolds...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28445745/increased-tissue-stiffness-in-tumors-from-mice-with-neurofibromatosis-1-optic-glioma
#4
Christopher Walter, Lindsey Crawford, Melinda Lai, Joseph A Toonen, Yuan Pan, Shelly Sakiyama-Elbert, David H Gutmann, Amit Pathak
Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#5
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445719/kat-independent-gene-regulation-by-tip60-promotes-esc-self-renewal-but-not-pluripotency
#6
Diwash Acharya, Sarah J Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A Rivera-Pérez, Thomas G Fazzio
Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445500/sf3b1-is-a-stress-sensitive-splicing-factor-that-regulates-both-hsf1-concentration-and-activity
#7
Karen S Kim Guisbert, Eric Guisbert
The heat shock response (HSR) is a well-conserved, cytoprotective stress response that activates the HSF1 transcription factor. During severe stress, cells inhibit mRNA splicing which also serves a cytoprotective function via inhibition of gene expression. Despite their functional interconnectedness, there have not been any previous reports of crosstalk between these two pathways. In a genetic screen, we identified SF3B1, a core component of the U2 snRNP subunit of the spliceosome, as a regulator of the heat shock response in Caenorhabditis elegans...
2017: PloS One
https://www.readbyqxmd.com/read/28445477/mitochondrial-respiration-in-highly-aerobic-canines-in-the-non-raced-state-and-after-a-1600-km-sled-dog-race
#8
Benjamin Miller, Karyn Hamilton, Robert Boushel, Katherine Williamson, Verena Laner, Erich Gnaiger, Michael Davis
At the annual Iditarod Race, Alaskan Huskies repeatedly run for up to 8 hours at 16 km/h to complete 1600 km. We previously demonstrated high rates of mitochondrial protein synthesis in Alaskan Huskies, which we suspected allowed rapid remodeling of mitochondrial proteins in response to energetic stress. The purpose of this study was to examine mitochondrial respiration in permeabilized skeletal muscle fibers of Alaskan Huskies in the offseason (Non-raced) and following the 1600 km Iditarod Sled Dog Race (Raced)...
2017: PloS One
https://www.readbyqxmd.com/read/28445461/tumour-ischaemia-by-interferon-%C3%AE-resembles-physiological-blood-vessel-regression
#9
Thomas Kammertoens, Christian Friese, Ainhoa Arina, Christian Idel, Dana Briesemeister, Michael Rothe, Andranik Ivanov, Anna Szymborska, Giannino Patone, Severine Kunz, Daniel Sommermeyer, Boris Engels, Matthias Leisegang, Ana Textor, Hans Joerg Fehling, Marcus Fruttiger, Michael Lohoff, Andreas Herrmann, Hua Yu, Ralph Weichselbaum, Wolfgang Uckert, Norbert Hübner, Holger Gerhardt, Dieter Beule, Hans Schreiber, Thomas Blankenstein
The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ-GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445262/dose-dependence-of-pth-related-peptide-1-on-the-osteogenic-induction-of-mc3t3-e1-cells-in-vitro
#10
Jianping Wang, Jingfeng Li, Liang Yang, Yichi Zhou, Yi Wang
Parathyroid hormone (PTH), an 84-amino acid peptide, is an endocrine hormone that is secreted by parathyroid glands. PTH performs important functions in calcium regulation and bone remodeling. The PTH (1-34) named teriparatide, a 34-amino acid peptide derived from the N-terminus of PTH, conserves most of the functions of PTH, specifically the osteogenic capability. However, teriparatide is only used by injection and exhibits short duration. In addition, this PTH could not thoroughly expose active sites. In this study, a novel PTH-related peptide (designated PTHrP-1) derived from the N-terminus of PTH was added into the complete medium at different concentrations of PTHrP-1 (0, 50, 100, and 200 ng/mL) to induce the MC3T3-E1 cells...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28444928/antiinflammatory-activity-of-cinnamon-cinnamomum-zeylanicum-bark-essential-oil-in-a-human-skin-disease-model
#11
Xuesheng Han, Tory L Parker
The effect of cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) on human skin cells has not been elucidated. Therefore, we investigated the activity of a commercially available CBEO in a validated human dermal fibroblast system, a model of chronic inflammation and fibrosis. We first evaluated the impact of CBEO on 17 protein biomarkers that play critical roles in inflammation and tissue remodeling. The impact of CBEO on genome-wide gene expression was also evaluated. CBEO showed strong anti-proliferative effects on skin cells and significantly inhibited the production of several inflammatory biomarkers, including vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interferon gamma-induced protein 10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by gamma interferon...
April 26, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28444909/the-histone-methyltransferase-ezh2-is-a-therapeutic-target-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type
#12
Yemin Wang, Shary Yuting Chen, Anthony N Karnezis, Shane Colborne, Nancy Dos Santos, Jessica D Lang, William P D Hendricks, Krystal A Orlando, Damian Yap, Friedrich Kommoss, Marcel B Bally, Gregg B Morin, Jeffrey M Trent, Bernard E Weissman, David G Huntsman
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but aggressive and untreatable malignancy affecting young women. We and others recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF chromatin-remodeling complex, is the only gene recurrently mutated in the majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the prominent role of the SWI/SNF chromatin-remodeling complex in transcriptional control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for oncogenic transformation...
April 26, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28444807/rkip-lessons-of-a-better-way-for-%C3%AE-adrenergic-receptor-activation-in-the-heart
#13
Kristina Lorenz, Marsha Rich Rosner, Theresa Brand, Joachim P Schmitt
Stimulation of β-adrenergic receptors (βAR) provides the most efficient physiological mechanism to enhance contraction and relaxation of the heart. Activation of βAR allows rapid enhancement of myocardial function in order to fuel the muscles for running and fighting in a fight-or-flight response. Likewise, βAR get activated during cardiovascular disease in an attempt to counteract the restrictions of cardiac output. However, long-term stimulation of βAR increases the likelihood of cardiac arrhythmias, adverse ventricular remodelling, decline of cardiac performance and premature death, thereby limiting the use of βAR agonists in the treatment of heart failure...
April 26, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28444455/prevalence-predictors-and-prognostic-implications-of-residual-impairment-of-functional-capacity-after-transcatheter-aortic-valve-implantation
#14
Mohammad Abdelghani, Rafael Cavalcante, Yosuke Miyazaki, Robbert J de Winter, Rogério Sarmento-Leite, José A Mangione, Alexandre Abizaid, Pedro A Lemos, Patrick W Serruys, Fabio S de Brito
BACKGROUND: Patients with degenerative aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) typically have advanced cardiac and vascular adverse remodeling and multiple comorbidities and, therefore, might not recover a normal functional capacity after valve replacement. We sought to investigate the prevalence, the predictors, and the prognostic impact of residual impairment of functional capacity after TAVI. METHODS AND RESULTS: Out of 790 patients undergoing TAVI with impaired functional capacity (NYHA II-IV) at baseline, NYHA functional class improved in 592 (86...
April 25, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28444195/dna-methylome-analysis-reveals-distinct-epigenetic-patterns-of-ascending-aortic-dissection-and-bicuspid-aortic-valve
#15
Sun Pan, Hao Lai, Yiru Shen, Charles Breeze, Stephan Beck, Tao Hong, Chunsheng Wang, Andrew E Teschendorff
Epigenetics may mediate the effects of environmental risk factors on disease, including heart disease. Thus, measuring the DNA methylome offers the opportunity to identify novel disease biomarkers and novel insights into disease mechanisms. The DNA methylation landscape of ascending aortic dissection (AD) and bicuspid aortic valve (BAV) with aortic aneurysmal dilatation remain uncharacterized. The present study aimed to explore the genome-wide DNA methylation landscape underpinning these two diseases. Methods and results: We used Illumina 450k DNA methylation beadarrays to analyze 21 ascending aorta samples, including 10 cases with AD, 5 with BAV and 6 healthy controls...
April 19, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28444180/left-bundle-branch-block-from-cardiac-mechanics-to-clinical-and-diagnostic-challenges
#16
Elena Surkova, Luigi P Badano, Roberto Bellu, Patrizia Aruta, Federica Sambugaro, Gabriella Romeo, Federico Migliore, Denisa Muraru
Left bundle branch block (LBBB) results in an altered pattern of left ventricular (LV) activation and subsequent contraction, causing remarkable changes in LV mechanics, perfusion and workload and ultimately leading to pathologic cardiac remodelling. Clinical and diagnostic notions about the LBBB phenomenon had evolved from just an electrocardiographic pattern to a critically important finding affecting diagnostic and clinical management of many patients and adversely influencing their outcomes. Recent advances in imaging techniques significantly improved the assessment of patients with LBBB and provided additional insights into pathophysiological mechanisms of LV remodelling...
April 20, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28444133/increased-collagen-within-the-transverse-tubules-in-human-heart-failure
#17
David J Crossman, Xin Shen, Mia Jüllig, Michelle Munro, Yufeng Hou, Martin Middleditch, Darshan Shrestha, Amy Li, Sean Lal, Cristobal G Dos Remedios, David Baddeley, Peter N Ruygrok, Christian Soeller
Aims: In heart failure transverse-tubule (t-tubule) remodelling disrupts calcium release, and contraction. T-tubules in human failing hearts exhibit increased labelling by wheat germ agglutinin (WGA), a lectin that binds to the dystrophin-associated glycoprotein complex. We hypothesized changes in this complex may explain the increased WGA labelling and contribute to t-tubule remodelling in the failing human heart. In this study we sought to identify the molecules responsible for this increased WGA labelling...
April 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28444108/racial-ethnic-differences-in-left-ventricular-structure-and-function-in-chronic-kidney-disease-the-chronic-renal-insufficiency-cohort
#18
Faraz S Ahmad, Xuan Cai, Katherine Kunkel, Ana C Ricardo, James P Lash, Dominic S Raj, Jiang He, Amanda H Anderson, Matthew J Budoff, Julie A Wright Nunes, Jason Roy, Jackson T Wright, Alan S Go, Martin G St John Sutton, John W Kusek, Tamara Isakova, Myles Wolf, Martin G Keane
BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. METHODS: In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity...
April 24, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28444013/third-molars-and-premolars-extraction-in-conventional-orthodontics-and-in-treatments-based-on-maxillary-bone-remodeling-with-temporary-anchorage-indications-and-care
#19
Alberto Consolaro
A bone is an anatomic structure in constant remodeling, with different, mutant and wonderfully inconstant designs. With every new and immediate functional demand, there are changes in cortical thickness, trabecular bone density and also in direction and size of trabeculae. Bones' non-stopping search is for adjusting to the functions induced by forces and movements required by a certain life style. Conventional orthodontic planning or with temporary anchorage based on bone remodeling takes into consideration the spaces that are - or may be - occupied by the teeth, in the formation of a functional and esthetic dental arch for the patient...
February 2017: Dental Press Journal of Orthodontics
https://www.readbyqxmd.com/read/28443954/mmp-9-levels-and-imt-of-carotid-arteries-are-elevated-in-obese-children-and-adolescents-compared-to-non-obese
#20
Claudio Andrade, Adriana Bosco, Valeria Sandrim, Francisco Silva
BACKGROUND: Childhood obesity is associated with increased risk of atherosclerosis and cardiovascular disease in adulthood. Increased intima-media thickness (IMT) of the carotid artery is linked to the initiation and progression of the chronic inflammatory processes implicated in cardiovascular disease. Matrix metalloproteinase-9 (MMP-9) plays an important role in the degradation of the extracellular matrix and, consequently, in the development, morphogenesis, repair and remodeling of connective tissues...
March 2017: Arquivos Brasileiros de Cardiologia
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