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Fibrosis AND Pirfenidone

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https://www.readbyqxmd.com/read/28091615/pirfenidone-controls-the-feedback-loop-of-the-at1r-p38-mapk-renin-angiotensin-system-axis-by-regulating-liver-x-receptor-%C3%AE-in-myocardial-infarction-induced-cardiac-fibrosis
#1
Chunmei Li, Rui Han, Le Kang, Jianping Wang, Yonglin Gao, Yanshen Li, Jie He, Jingwei Tian
Pirfenidone (PFD), an anti-fibrotic small molecule drug, is used to treat fibrotic diseases, but its effects on myocardial infarction (MI)-induced cardiac fibrosis are unknown. The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-α (LXR-α) expression...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079978/targeting-coagulation-factor-receptors-protease-activated-receptors-in-idiopathic-pulmonary-fibrosis
#2
REVIEW
Cong Lin, Keren Borensztajn, C Arnold Spek
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a 5-year mortality rate above 50% and unknown etiology. Treatment options remain limited and, currently, only two drugs are available, nintedanib and pirfenidone. However, both of these antifibrotic agents only slow down the progression of the disease but do not remarkably prolong the survival of IPF patients. Hence, the discovery of new therapeutic targets for IPF is crucial. Studies exploring the mechanisms that are involved in IPF identified several possible targets for therapeutic interventions...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28054535/combined-prednisolone-and-pirfenidone-in-bleomycin-induced-lung-disease
#3
Preyas J Vaidya, H S Sandeepa, Tejinder Singh, S K Susheel Kumar, Rajat Bhargava, Gopal Ramakrishnan, Prashant N Chhajed
Bleomycin is a cytostatic drug commonly employed in the treatment of Hodgkin's disease, seminomas, and choriocarcinoma. Bleomycin may induce a chronic pulmonary inflammation that may progress to fibrosis. So far, only corticosteroids have been used in the treatment of bleomycin-induced lung disease with variable results. Pirfenidone is an antifibrotic drug that has been approved for the treatment of idiopathic pulmonary fibrosis. We report two cases of bleomycin-induced lung disease treated successfully with pirfenidone and oral corticosteroids...
July 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28039616/a-cost-effectiveness-analysis-of-nintedanib-in-idiopathic-pulmonary-fibrosis-in-the-uk
#4
C Rinciog, M Watkins, S Chang, T M Maher, C LeReun, D Esser, A Diamantopoulos
BACKGROUND: International guidelines recommend nintedanib (OFEV(®)) as an option for the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective. METHODS: A Markov model was designed to capture the changes in the condition of adults with IPF...
December 31, 2016: PharmacoEconomics
https://www.readbyqxmd.com/read/28035951/a-systematic-review-of-the-role-of-dysfunctional-wound-healing-in-the-pathogenesis-and-treatment-of-idiopathic-pulmonary-fibrosis
#5
REVIEW
Alan Betensley, Rabab Sharif, Dimitrios Karamichos
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments...
December 26, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28012488/prognostic-value-of-serial-serum-kl-6-measurements-in-patients-with-idiopathic-pulmonary-fibrosis
#6
Kentaro Wakamatsu, Nobuhiko Nagata, Hiroyuki Kumazoe, Keishi Oda, Hiroshi Ishimoto, Michihiro Yoshimi, Shohei Takata, Minako Hamada, Yoshifusa Koreeda, Kouji Takakura, Miwa Ishizu, Makiko Hara, Shinji Ise, Miiru Izumi, Takashi Akasaki, Sanae Maki, Masaharu Kawabata, Hiroshi Mukae, Masayuki Kawasaki
BACKGROUND: The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS: Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC)...
January 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/27971558/cost-effectiveness-analysis-of-pirfenidone-for-the-treatment-of-mild-to-moderate-idiopathic-pulmonary-fibrosis-ipf-compared-to-best-supportive-care-and-nintedanib-from-the-italian-nhs-perspective
#7
R Ravasio, M Ferrario, M Pata, P Thuresson
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27939076/efficacy-of-simtuzumab-versus-placebo-in-patients-with-idiopathic-pulmonary-fibrosis-a-randomised-double-blind-controlled-phase-2-trial
#8
Ganesh Raghu, Kevin K Brown, Harold R Collard, Vincent Cottin, Kevin F Gibson, Robert J Kaner, David J Lederer, Fernando J Martinez, Paul W Noble, Jin Woo Song, Athol U Wells, Timothy P M Whelan, Wim Wuyts, Emmanuel Moreau, Scott D Patterson, Victoria Smith, Selina Bayly, Jason W Chien, Qi Gong, Jenny J Zhang, Thomas G O'Riordan
BACKGROUND: Lysyl oxidase-like 2 (LOXL2) catalyses collagen cross-linking and is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the efficacy and safety of simtuzumab, a monoclonal antibody against LOXL2, in patients with IPF. METHODS: In this randomised, double-blind, phase 2 trial, we recruited patients aged 45-85 years with definite IPF diagnosed prior to 3 years of screening from 183 hospitals and respiratory clinics in 14 countries...
January 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27937011/effects-and-mechanisms-of-pirfenidone-prednisone-and-acetylcysteine-on-pulmonary-fibrosis-in-rat-idiopathic-pulmonary-fibrosis-models
#9
Wencheng Yu, Fang Guo, Xiaoxia Song
CONTEXT: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. OBJECTIVE: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. MATERIALS AND METHODS: Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27876248/pirfenidone-and-mortality-in-idiopathic-pulmonary-fibrosis
#10
Paolo Spagnolo
No abstract text is available yet for this article.
January 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27876247/effect-of-pirfenidone-on-mortality-pooled-analyses-and-meta-analyses-of-clinical-trials-in-idiopathic-pulmonary-fibrosis
#11
Steven D Nathan, Carlo Albera, Williamson Z Bradford, Ulrich Costabel, Ian Glaspole, Marilyn K Glassberg, David R Kardatzke, Monica Daigl, Klaus-Uwe Kirchgaessler, Lisa H Lancaster, David J Lederer, Carlos A Pereira, Jeffrey J Swigris, Dominique Valeyre, Paul W Noble
BACKGROUND: In clinical trials of idiopathic pulmonary fibrosis, rates of all-cause mortality are low. Thus prospective mortality trials are logistically very challenging, justifying the use of pooled analyses or meta-analyses. We did pooled analyses and meta-analyses of clinical trials of pirfenidone versus placebo to determine the effect of pirfenidone on mortality outcomes over 120 weeks. METHODS: We did a pooled analysis of the combined patient populations of the three global randomised phase 3 trials of pirfenidone versus placebo-Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72-120 weeks) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND 016; 52 weeks)-for all-cause mortality, treatment-emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality, and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks 52, 72, and 120...
January 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27871152/human-adipose-derived-mesenchymal-stem-cells-attenuate-early-stage-of-bleomycin-induced-pulmonary-fibrosis-comparison-with-pirfenidone
#12
Manoj Reddy, Lyle Fonseca, Shashank Gowda, Basavraj Chougule, Aarya Hari, Satish Totey
Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, invariably fatal fibrotic lung disease with no lasting option for therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the treatment of IPF. Aim of the study was to investigate improvement in survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced pulmonary fibrosis model. Methods: Human AD-MSCs were administered intravenously on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas, pirfenidone was given orally in drinking water at the rate of 100 mg/kg body weight three times a day daily from day 3 onward...
November 30, 2016: International Journal of Stem Cells
https://www.readbyqxmd.com/read/27863518/safety-and-efficacy-of-bridging-to-lung-transplantation-with-antifibrotic-drugs-in-idiopathic-pulmonary-fibrosis-a-case-series
#13
Isabelle Delanote, Wim A Wuyts, Jonas Yserbyt, Eric K Verbeken, Geert M Verleden, Robin Vos
BACKGROUND: Following recent approval of pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF), questions arise about the use of these antifibrotics in patients awaiting lung transplantation (LTx). METHODS: Safety and efficacy of antifibrotic drugs in IPF patients undergoing LTx were investigated in a single-centre retrospective cohort analysis. RESULTS: A total of nine patients, receiving antifibrotic therapy for 419 ± 315 days until subsequent LTx, were included...
November 18, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27862475/treatment-of-idiopathic-pulmonary-fibrosis-a-position-paper-from-a-nordic-expert-group
#14
REVIEW
C M Sköld, E Bendstrup, M Myllärniemi, G Gudmundsson, T Sjåheim, O Hilberg, A Altraja, R Kaarteenaho, G Ferrara
Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients...
November 13, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27858160/assessing-the-therapeutic-response-to-pirfenidone-in-idiopathic-pulmonary-fibrosis-can-we-do-better-than-with-forced-vital-capacity-alone
#15
Karishma Hosein, Jamie Le, Marco Mura
New anti-fibrotic agents for idiopathic pulmonary fibrosis (IPF) were approved based on the results of forced vital capacity (FVC) trends, although concerns were raised about the reliability of FVC as the only endpoint parameter. We hypothesized that IPF-specific multi-dimensional scores (Composite Physiologic Index-CPI; gender-age-physiology-GAP; risk stratification score-RISE) would better capture response to therapy. In this pilot study, treated and untreated cohorts of IPF patients, matched for demographic and functional characteristics were prospectively followed for 1 year, at 4-month intervals...
November 17, 2016: Lung
https://www.readbyqxmd.com/read/27835939/anti-fibrotic-action-of-pirfenidone-in-dupuytren-s-disease-derived-fibroblasts
#16
Chaoming Zhou, Fang Liu, Phillip H Gallo, Mark E Baratz, Sandeep Kathju, Latha Satish
BACKGROUND: Dupuytren's disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren's fibrosis...
November 11, 2016: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/27812432/treatment-of-rapidly-progressive-systemic-sclerosis-current-and-futures-perspectives
#17
Fabian A Mendoza, Maryah Mansoor, Sergio A Jimenez
INTRODUCTION: Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. AREAS COVERED: This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification...
2016: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/27788604/pirfenidone-exerts-a-suppressive-effect-on-ccl18-expression-in-u937-derived-macrophages-partly-by-inhibiting-stat6-phosphorylation
#18
Yoshinobu Saito, Arata Azuma, Kuniko Matsuda, Koichiro Kamio, Shinji Abe, Akihiko Gemma
CONTEXT: CC chemokine ligand 18 (CCL18) is suggested to play a role in the development of pulmonary fibrosis. Macrophages are thought to be the main source of CCL18, and the effect of pirfenidone, an anti-fibrotic agent for idiopathic pulmonary fibrosis, on the expression of CCL18 in macrophages warrants investigation. OBJECTIVE: The purpose of this study was to investigate the effect of pirfenidone on the expression of CCL18 in macrophages. MATERIALS AND METHODS: U937 cells were differentiated into macrophages by phorbol myristate acetate and then stimulated with recombinant IL-4 to induce the production of CCL18...
October 27, 2016: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27756881/targeting-the-cancer-associated-fibroblasts-as-a-treatment-in-triple-negative-breast-cancer
#19
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27735147/role-of-pirfenidone-in-idiopathic-pulmonary-fibrosis-a-longitudinal-cohort-study
#20
K P Suraj, Neethu K Kumar, E Jyothi, Kiran Vishnu Narayan, G Biju
BACKGROUND: But so far there is no proven pharmacological treatment for Idiopathic pulmonary fibrosis (IPF). As trials investigating different agents with different mechanisms of actions are going on, encouraging results have led to the licensing of the first IPF-specific drug, Pirfenidone. OBJECTIVE: To assess the proportion of IPF among interstitial lung disease patients and to assess their treatment response to Pirfenidone. MATERIAL AND METHODS: All consecutive patients attending the outpatient department from 1st January 2012 to 30th June 2012 with a proven diagnosis of Interstitial lung Disease (ILD) were included in this longitudinal cohort study...
May 2016: Journal of the Association of Physicians of India
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