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https://www.readbyqxmd.com/read/27886639/hyaluronan-derived-swelling-of-solid-tumors-the-contribution-of-collagen-and-cancer-cells-and-implications-for-cancer-therapy
#1
Chrysovalantis Voutouri, Christiana Polydorou, Panagiotis Papageorgis, Vasiliki Gkretsi, Triantafyllos Stylianopoulos
Despite the important role that mechanical forces play in tumor growth and therapy, the contribution of swelling to tumor mechanopathology remains unexplored. Tumors rich in hyaluronan exhibit a highly negative fixed charge density. Repulsive forces among these negative charges as well as swelling of cancer cells due to regulation of intracellular tonicity can cause tumor swelling and development of stress that might compress blood vessels, compromising tumor perfusion and drug delivery. Here, we designed an experimental strategy, using four orthotopic tumor models, to measure swelling stress and related swelling to extracellular matrix components, hyaluronan and collagen, as well as to tumor perfusion...
November 21, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27876248/pirfenidone-and-mortality-in-idiopathic-pulmonary-fibrosis
#2
Paolo Spagnolo
No abstract text is available yet for this article.
November 18, 2016: 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
#3
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...
November 19, 2016: 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
#4
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
#5
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
#6
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
#7
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
#8
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/27821905/combined-effects-of-drugs-and-plasticizers-on-the-properties-of-drug-delivery-films
#9
Cheryl L Jennings, Thomas D Dziubla, David A Puleo
Formation of scar tissue may be reduced or prevented if wounds were locally treated with a combination of molecules tuned to the different healing phases, guiding tissue regeneration along a scar free path. To this end, drug delivery devices made of cellulose acetate phthalate and Pluronic F-127 were loaded with either quercetin or pirfenidone and plasticized with either triethyl citrate (TEC) or tributyl citrate (TBC). Quercetin inhibits oxidative stress, and pirfenidone has been shown to reduce production of pro-inflammatory and fibrogenic molecules...
July 2016: Journal of Bioactive and Compatible Polymers
https://www.readbyqxmd.com/read/27812432/treatment-of-rapidly-progressive-systemic-sclerosis-current-and-futures-perspectives
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27734496/pirfenidone-ameliorates-concanavalin-a-induced-hepatitis-in-mice-via-modulation-of-reactive-oxygen-species-nuclear-factor-kappa-b-signalling-pathways
#14
Dina S El-Agamy
OBJECTIVES: This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice. METHODS: Autoimmune model of hepatitis was established using single intravenous injection of Con A. Mice were randomly assigned into four groups as follows: control group; Con A group; and two groups, receiving PFD in two dose levels (200, 300 mg/kg) for 5 days before Con A administration. Extent of hepatitis was studied using biochemical, histopathological and immunohistochemical estimations...
December 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27715339/effect-of-pirfenidone-on-vascular-proliferation-inflammation-and-fibrosis-in-an-abdominal-adhesion-rat-model
#15
Pinar Solmaz Hasdemir, Mahmud Ozkut, Tevfik Guvenal, Melis Aylin Uner, Esat Calik, Semra Oruc Koltan, Faik Mumtaz Koyuncu, Kemal Ozbilgin
AIM: To study the efficacy of pirfenidone for prevention of postoperative adhesion formation in an adhesion rat model. MATERIALS AND METHODS: Eighteen female Wistar rats were subjected to right-sided parietal peritoneum and right uterine horn adhesion model. Rats were randomized into three groups: group 1 (control) (closure of midline abdominal incision without any agent administration), group 2 (closure of incision after intraperitoneal administration of pirfenidone), and group 3 (closure of incision and only oral administration of pirfenidone for 14 days)...
August 15, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/27708114/effect-of-statins-on-disease-related-outcomes-in-patients-with-idiopathic-pulmonary-fibrosis
#16
Michael Kreuter, Francesco Bonella, Toby M Maher, Ulrich Costabel, Paolo Spagnolo, Derek Weycker, Klaus-Uwe Kirchgaessler, Martin Kolb
BACKGROUND: Data are conflicting regarding the possible effects of statins in patients with idiopathic pulmonary fibrosis (IPF). This post hoc analysis assessed the effects of statin therapy on disease-related outcomes in IPF. METHODS: Patients randomised to placebo (n=624) in three controlled trials of pirfenidone in IPF (CAPACITY 004 and 006, ASCEND) were categorised by baseline statin use. Outcomes assessed during the 1-year follow-up included disease progression, mortality, hospitalisation and composite outcomes of death or ≥10% absolute decline in FVC and death or ≥50 m decline in 6-minute walk distance (6MWD)...
October 5, 2016: Thorax
https://www.readbyqxmd.com/read/27699232/the-antifibrotic-drug-pirfenidone-promotes-pulmonary-cavitation-and-drug-resistance-in-a-mouse-model-of-chronic-tuberculosis
#17
Bintou A Ahidjo, Mariama C Maiga, Elizabeth A Ihms, Mamoudou Maiga, Alvaro A Ordonez, Laurene S Cheung, Sarah Beck, Bruno B Andrade, Sanjay Jain, William R Bishai
Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone's antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response...
September 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27660413/preparation-of-novel-pirfenidone-microspheres-for-lung-targeted-delivery-in-vitro-and-in-vivo-study
#18
Dianbo Li, Liping Gong
The aim of this study was to develop and characterize pirfenidone (PF)-loaded chitosan microspheres for lung targeting. The microspheres were prepared using the emulsion-solvent evaporation method and characterized by assessing morphology, particle size, and zeta potential. The microspheres had a spherical nature with highly smooth and integrated surfaces. The particle size of microspheres was 4.6±0.3 µm, and the zeta potential was 20.3±1.4 mV. The in vitro release results indicated that the obtained formulation of PF could reach the state of sustained release with a biphasic drug release pattern...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27616539/pirfenidone-treatment-in-idiopathic-pulmonary-fibrosis-nationwide-danish-results
#19
Goran Nadir Salih, Saher Burhan Shaker, Helle Dall Madsen, Elisabeth Bendstrup
BACKGROUND: Pirfenidone was approved by the European Medicines Agency and introduced in most European countries in 2011 for treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To describe the national Danish experiences of pirfenidone treatment for IPF during 30 months with respect to target population, safety, adherence to the treatment and effect analysis in a well-characterised IPF population in a real-life setting. METHODS: Retrospective data collection from medical records of all patients in Denmark with IPF from 2011 to 2014...
2016: European Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27615411/pirfenidone-in-patients-with-rapidly-progressive-interstitial-lung-disease-associated-with-clinically-amyopathic-dermatomyositis
#20
Ting Li, Li Guo, Zhiwei Chen, Liyang Gu, Fangfang Sun, Xiaoming Tan, Sheng Chen, Xiaodong Wang, Shuang Ye
To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants...
September 12, 2016: Scientific Reports
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