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https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#1
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420224/silk-fibroin-alginate-hydroxyapatite-composite-particles-in-bone-tissue-engineering-applications-in-vivo
#2
You-Young Jo, Seong-Gon Kim, Kwang-Jun Kwon, HaeYong Kweon, Weon-Sik Chae, Won-Geun Yang, Eun-Young Lee, Hyun Seok
The aim of this study was to evaluate the in vivo bone regeneration capability of alginate (AL), AL/hydroxyapatite (HA), and AL/HA/silk fibroin (SF) composites. Forty Sprague Dawley rats were used for the animal experiments. Central calvarial bone (diameter: 8.0 mm) defects were grafted with AL, AL/HA, or AL/HA/SF. New bone formation was evaluated by histomorphometric analysis. To demonstrate the immunocompatibility of each group, the level of tumor necrosis factor (TNF)-α expression was studied by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) at eight weeks post implantation...
April 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419560/fibroblast-growth-factor-23-concentration-in-dogs-with-chronic-kidney-disease
#3
L M Harjes, V J Parker, K Dembek, G S Young, L H Giovaninni, M M Kogika, D J Chew, R E Toribio
BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism. This syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is an early biomarker of CKD in people. It is an independent risk factor for both progression of renal disease and survival time in humans and cats with CKD. Information about FGF-23 in healthy dogs and those with CKD is lacking...
April 17, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28415155/letter-to-the-editor-regarding-dounousi-e-et%C3%A2-al-intact-fgf23-and-%C3%AE-klotho-during-acute-inflammation-sepsis-in-ckd-patients-eur-j-clin-invest-2016-46-234-41
#4
Axel Schlitt, Urban Sester, Martina Sester, Sarah Seiler-Mussler, Vincent Brandenburg, Elke Schäffner, Gunnar H Heine
With interest we read the recent European Journal of Clinical Investigation paper entitled "Intact FGF23 and α-Klotho during acute inflammation/sepsis in CKD patients" by E. Dounousi and coworkers (1). In their article, the authors analyse the association between acute infection and plasma levels of the phosphaturic hormone fibroblast growth factor 23 (FGF-23). The physiological regulation of FGF-23 is not fully understood so far, and hence novel pathophysiological data are of importance. Particularly the link between FGF23 and inflammation is a growing field...
April 17, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28406928/fibroblast-growth-factor-23-promotes-terminal-differentiation-of-atdc5-cells
#5
Mathilde Guibert, Adeline Gasser, Hervé Kempf, Arnaud Bianchi
OBJECTIVES: Fibroblast Growth Factor 23 (FGF23) is well documented as a crucial player in the systemic regulation of phosphate homeostasis. Moreover, loss-of-function experiments have revealed that FGF23 also has a phosphate-independent and local impact on skeletogenesis. Here, we used ATDC5 cell line to investigate the expression of FGF23 and the role it may play locally during the differentiation of these cells. METHODS: ATDC5 cells were differentiated in the presence of insulin, and treated with recombinant FGF23 (rFGF23), inorganic phosphate (Pi) and/or PD173074, an inhibitor of FGF receptors (FGFRs)...
2017: PloS One
https://www.readbyqxmd.com/read/28402974/cardiac-changes-and-their-association-with-fetuin-a-and-fibroblast-growth-factor-23-in-children-with-chronic-kidney-disease
#6
Abdullahi Mudi, Hopewell Ntsinjana, Caroline Dickens, Cecil Levy, Daynia Ballot
AIMS: In children with chronic kidney disease (CKD), fetuin-A and fibroblast growth factor-23 (FGF-23) have been implicated in the mechanism and progression of several cardiac changes. This study aimed to determine the types and rates of cardiac changes in children with CKD and their association with fetuin-A, FGF-23, and other cardiovascular risk factors (CVRFs). METHODS: This comparative cross-sectional study recruited 88 children (5-18 years): 27 CKD I with a glomerular filtration rate (GFR) >90 mL/min/1...
April 13, 2017: Nephron
https://www.readbyqxmd.com/read/28402487/circulating-klotho-associates-with-cardiovascular-morbidity-and-mortality-during-hemodialysis
#7
Christophe Marçais, Delphine Maucort-Boulch, Jocelyne Drai, Emmanuelle Dantony, Marie-Christine Carlier, Emilie Blond, Leslie Genet, François Kuentz, Dominique Lataillade, Eric Legrand, Xavier Moreau-Gaudry, Guillaume Jean, Denis Fouque
Background: Klotho gene was identified as an aging suppressor. In animals klotho over-expression extends lifespan and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels and during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well. Objective: We aimed to determine the consequences of a serum klotho defect on cardiovascular morbidity and mortality during chronic dialysis...
April 11, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28401422/acetate-free-biofiltration-to-remove-fibroblast-growth-factor-23-in-hemodialysis-patients-a-pilot-study
#8
Valeria Cernaro, Silvia Lucisano, Valeria Canale, Annamaria Bruzzese, Daniela Caccamo, Giuseppe Costantino, Michele Buemi, Domenico Santoro
AIM: Serum levels of 32 kDa-phosphaturic hormone fibroblast growth factor 23 (FGF23) rise early in renal failure in order to keep phosphatemia within the normal range; however, this compensatory mechanism itself contributes to chronic kidney disease-mineral bone disorder. High FGF23 is also associated to left ventricular hypertrophy, vascular calcifications and thus increased cardiovascular risk. The aim of this pilot pre-post study was to evaluate the effects of a single hemodiafiltration session with acetate-free biofiltration (AFB) on FGF23 serum levels...
April 11, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28377558/pentraxin-3-as-a-new-indicator-of-cardiovascular%C3%A2-related-death-in-patients-with-advanced-chronic-kidney-disease
#9
Marcin Krzanowski, Katarzyna Krzanowska, Mariusz Gajda, Paulina Dumnicka, Artur Dziewierz, Karolina Woziwodzka, Jan A Litwin, Władysław Sułowicz
INTRODUCTION    Pentraxin3 (PTX3) play an important role in the inflammatory response, taking part in recognizing pathogens and damaged tissues. OBJECTIVES    The aim of the study was to assess the relationship between PTX3 levels and all-cause and cardiovascular (CV) mortality in chronic kidney disease (CKD) patients during five-year observation period.  PATIENTS AND METHODS    The study comprised 78 patients (51 hemodialyzed, 27 predialysis). The examined parameters included PTX3, calcium, phosphate, iPTH, interleukin-6 (IL-6), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin, tumor necrosis factor receptor II (TNF-R II), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), stromal cell-derived factor α (SDF1α), and thrombomodulin (TM)...
February 27, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28361317/generation-of-gastrointestinal-organoids-from-human-pluripotent-stem-cells
#10
Jorge O Múnera, James M Wells
Over the past several decades, developmental biologists have discovered fundamental mechanisms by which organs form in developing embryos. With this information it is now possible to generate human "organoids" by the stepwise differentiation of human pluripotent stem cells using a process that recapitulates organ development. For the gastrointestinal tract, one of the first key steps is the formation of definitive endoderm and mesoderm, a process that relies on the TGFb molecule Nodal. Endoderm is then patterned along the anterior-posterior axis, with anterior endoderm forming the foregut and posterior endoderm forming the mid and hindgut...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28346348/vitamin-d-in-chronic-kidney-disease-and-dialysis-patients
#11
REVIEW
Guillaume Jean, Jean Claude Souberbielle, Charles Chazot
Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue...
March 25, 2017: Nutrients
https://www.readbyqxmd.com/read/28341272/kidney-fibroblast-growth-factor-23-does-not-contribute-to-elevation-of-its-circulating-levels-in-uremia
#12
Maria L Mace, Eva Gravesen, Anders Nordholm, Jacob Hofman-Bang, Thomas Secher, Klaus Olgaard, Ewa Lewin
Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia...
March 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28339837/vitamin-d-treatment-attenuates-cardiac-fgf23-fgfr4-signaling-and-hypertrophy-in-uremic-rats
#13
Maren Leifheit-Nestler, Alexander Grabner, Laura Hermann, Beatrice Richter, Karin Schmitz, Dagmar-Christiane Fischer, Christopher Yanucil, Christian Faul, Dieter Haffner
Background.: Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. Methods...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339804/intra-cardiac-and-peripheral-levels-of-biochemical-markers-of-fibrosis-in-patients-undergoing-catheter-ablation-for-atrial-fibrillation
#14
Gordon A Begg, Rashed Karim, Tobias Oesterlein, Lee N Graham, Andrew J Hogarth, Stephen P Page, Christopher B Pepper, Kawal Rhode, Gregory Y H Lip, Arun V Holden, Sven Plein, Muzahir H Tayebjee
Aims: Measurement of circulating biomarkers of fibrosis may have a role in selecting patients and treatment strategy for catheter ablation. Pro-collagen type III N-terminal pro-peptide (PIIINP), C-telopeptide of type I collagen (ICTP), fibroblast growth factor 23 (FGF-23), and galectin 3 (gal-3) have all been suggested as possible biomarkers for this indication, but studies assessing whether peripheral levels reflect intra-cardiac levels are scarce. Methods and results: We studied 93 patients undergoing ablation for paroxysmal atrial fibrillation (AF) (n = 63) or non-paroxysmal AF (n = 30)...
February 27, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28326350/tumor-induced-osteomalacia-secondary-to-anaplastic-thyroid-carcinoma-a-case-report-and-review-of-the-literature
#15
Ejigayehu G Abate, Victor Bernet, Cherise Cortese, Hillary W Garner
CONTEXT: Tumor induced osteomalacia related to anaplastic thyroid cancer has never been reported. OBJECTIVE: We describe a case of tumor induced osteomalacia (TIO) in a patient with a fibroblast growth factor 23 (FGF-23) secreting anaplastic thyroid carcinoma. The current imaging modalities are reviewed. DESIGN AND INTERVENTION: Clinical, biochemical, and radiological assessments were done, including computer tomography (CT) of the neck and skull to thigh positron emission tomography (PET)/CT...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28318623/the-complexity-of-chronic-kidney-disease-mineral-and-bone-disorder-across-stages-of-chronic-kidney%C3%A2-disease
#16
Fabiana G Graciolli, Katia R Neves, Fellype Barreto, Daniela V Barreto, Luciene M Dos Reis, Maria E Canziani, Yves Sabbagh, Aluizio B Carvalho, Vanda Jorgetti, Rosilene M Elias, Susan Schiavi, Rosa M A Moysés
Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28290186/phosphorus-and-other-aspects-of-ckd-mbd-in-the-conservative-management-of-chronic-kidney-disease
#17
Anuja Shah
As the prevalence of chronic kidney disease (CKD) increases and the population ages, there is an imperative to offer cost effective and patient specific therapeutic options for the management of advanced CKD. In cases where there is a desire to avoid or delay renal replacement therapy, conservative options need to be defined and strategies for delaying the need for renal replacement therapy should be offered. CKD-mineral bone disorders (MBD) refers to the constellation of disturbances in abnormal bone and soft tissue calcification along with abnormalities, in phosphorus, calcium, parathyroid hormone, vitamin D, and FGF-23...
June 2017: Panminerva Medica
https://www.readbyqxmd.com/read/28289333/influence-of-vaginal-lactoferrin-administration-on-amniotic-fluid-cytokines-and-its-role-against-inflammatory-complications-of-pregnancy
#18
Martina Maritati, Manola Comar, Nunzia Zanotta, Silva Seraceni, Alessandro Trentini, Fabrizio Corazza, Fortunato Vesce, Carlo Contini
BACKGROUND: An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Up to this date there is no exhaustive information neither on the foetal cytokine balance nor on the best method for its modulation. We aimed to evaluate the influence of vaginal lactoferrin administration on amniotic fluid concentration of 47 cytokines, chemokines and growth factors. METHODS: Sixty women undergoing genetic amniocentesis were enrolled in an open-label clinical trial...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28276325/ferric-carboxymaltose-induced-hypophosphataemia-after-kidney-transplantation
#19
V Sari, R Atiqi, E J Hoorn, A C Heijboer, T van Gelder, D A Hesselink
BACKGROUND: Ferric carboxymaltose (FCM) can induce hypophosphataemia in the general population and patients with chronic kidney disease (CKD). Less is known about the effect of FCM in the kidney transplant population. It has been suggested that fibroblast growth factor 23 (FGF-23)-mediated renal phosphate wasting may be the most likely cause of this phenomenon. In the current study, the effects of FCM on phosphate metabolism were studied in a cohort of kidney transplant recipients. METHODS: Two index patients receiving FCM are described...
March 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/28267132/pentraxin3-as-a-new-indicator-of-cardiovascular-related-death-in-patients-with-advanced-chronic-kidney-disease
#20
Marcin Krzanowski, Katarzyna Krzanowska, Mariusz Gajda, Paulina Dumnicka, Artur Dziewierz, Karolina Woziwodzka, Jan A Litwin, Władysław Sułowicz
INTRODUCTION    Pentraxin3 (PTX3) play an important role in the inflammatory response, taking part in recognizing pathogens and damaged tissues. OBJECTIVES    The aim of the study was to assess the relationship between PTX3 levels and all-cause and cardiovascular (CV) mortality in chronic kidney disease (CKD) patients during five-year observation period.  PATIENTS AND METHODS    The study comprised 78 patients (51 hemodialyzed, 27 predialysis). The examined parameters included PTX3, calcium, phosphate, iPTH, interleukin-6 (IL-6), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin, tumor necrosis factor receptor II (TNF-R II), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), stromal cell-derived factor α (SDF1α), and thrombomodulin (TM)...
February 27, 2017: Polish Archives of Internal Medicine
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