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TGF beta AND Pirfenidone

Qin Yang, Junke Wang, Fei Liu, Wenjie Ma, Haijie Hu, Congdun Ran, Fuyu Li, Qiuwei Pan
BACKGROUND: Benign biliary stricture (BBS) is highly refractory. Currently, there is no effective strategy for prevention of BBS recurrence. The aim of this study is to establish a novel BBS rabbit model and to investigate the efficacy of biliary infusion with anti-proliferative medications for treating BBS. METHOD: A BBS model was established via surgical injury and biliary infection. The biliary infusion tube was inserted into the common bile duct via the stump of cystic duct after cholecystectomy...
May 16, 2018: Digestive Diseases and Sciences
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
September 22, 2017: Oncotarget
Xueling He, Liang Li, Min Tang, Ye Zeng, Huiming Li, Xiaoqin Yu
Electrical conductance is one of the factors of the microenvironment of cardiomyocytes, and electrical stimulation (ES) has been shown to modulate the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) toward a cardiomyogenic fate. Transforming growth factor-beta 1 (TGF-β1) stimulates the cardiomyogenic marker expression in BMSCs. Herein, we promoted the differentiation of BMSCs into cardiomyocyte-like cells using ES to confirm if TGF-β1 mediates this event in vitro. ES increased protein levels of TGF-β1 in BMSCs, and this effect was better than that observed with 5-azacytidine (5-Aza)...
September 29, 2017: Progress in Biophysics and Molecular Biology
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
Rokhsana Rasooli, Hamid Rajaian, Abbas Pardakhty, Ali Mandegary
BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects...
February 2018: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
J Raúl Olmos-Zuñiga, Mariana Silva-Martínez, Rogelio Jasso-Victoria, Matilde Baltazares-Lipp, Claudia Hernández-Jiménez, Ivette Buendía-Roldan, Jazmin Jasso-Arenas, Alan Martínez-Salas, Jazmin Calyeca-Gómez, Axel E Guzmán-Cedillo, Miguel Gaxiola-Gaxiola, Laura Romero-Romero
Tracheal stenosis (TS) is a fibrosis originated by prolonged inflammation and increased transforming growth factor beta 1 (TGF- β 1) expression and collagen deposition (CD) in the tracheal wound. Several wound-healing modulators (WHMs) have been used to modulate the tracheal healing process and prevent TS, but they have failed, justifying the need to evaluate alternative WHM. The pirfenidone (PFD) and collagen-polyvinylpyrrolidone (Collagen-PVP) decrease inflammation and fibrosis. This study assessed the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF- β 1 expression, and CD in an experimental model of tracheal wound healing...
2017: BioMed Research International
Yuan Liu, Fuai Lu, Lirong Kang, Zhihua Wang, Yongfu Wang
BACKGROUND: Oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the expression level of antioxidant factors, further regulating the function of oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for IPF therapy approved drugs...
April 18, 2017: BMC Pulmonary Medicine
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
Zulfu Bayhan, Sezgin Zeren, Fatma Emel Kocak, Cengiz Kocak, Raziye Akcılar, Ertugrul Kargı, Cagrı Tiryaki, Faik Yaylak, Aydın Akcılar
BACKGROUND: Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage...
April 2016: Journal of Surgical Research
Lynda Aoudjehane, Pierre-Yves Boelle, Grégoire Bisch, Rolland Delelo, François Paye, Olivier Scatton, Chantal Housset, Jérôme Becquart, Yvon Calmus, Filomena Conti
We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2'-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0...
June 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Virgil A S H Dalm, Willem A Dik, Hok B Thio, Bernt van den Blink, P Martin van Hagen, Paul L A van Daele
Fibrosis is one of the leading causes of morbidity and mortality in the Western world. This disorder is characterised by an abnormal and increased rate of fibroblast proliferation and by an excessive deposition of connective tissue. The key player in fibrosis is the myofibroblast. Fibrosis leads to loss of organ structure and, eventually, to decrease in organ function. To date, there are hardly any effective therapies for the treatment of patients with fibrosis. Pirfenidone targets the myofibroblast and is effective in the treatment of idiopathic pulmonary fibrosis...
2015: Nederlands Tijdschrift Voor Geneeskunde
Seo-Hyun Choi, Jae-Kyung Nam, Junho Jang, Hae-June Lee, Yoon-Jin Lee
Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm³ increased collagen levels, particularly in large tumor vessels...
June 26, 2015: Biochemical and Biophysical Research Communications
Inge M Westra, Dorenda Oosterhuis, Geny M M Groothuis, Peter Olinga
Two important signaling pathways in liver fibrosis are the PDGF- and TGFβ pathway and compounds inhibiting these pathways are currently developed as antifibrotic drugs. Testing antifibrotic drugs requires large numbers of animal experiments with high discomfort. Therefore, a method to study these drugs ex vivo was developed using precision-cut liver slices from fibrotic rat livers (fPCLS), representing an ex vivo model with a multicellular fibrotic environment. We characterized the fibrotic process in fPCLS from rat livers after 3 weeks of bile duct ligation (BDL) during incubation and tested compounds predominantly inhibiting the TGFβ pathway (perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone) and PDGF pathway (imatinib, sorafenib and sunitinib)...
2014: PloS One
Enrico Conte, Elisa Gili, Evelina Fagone, Mary Fruciano, Maria Iemmolo, Carlo Vancheri
Pirfenidone is an orally active small molecule that has been shown to inhibit the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis. Although pirfenidone exhibits well documented antifibrotic and antiinflammatory activities, in vitro and in vivo, its molecular targets and mechanisms of action have not been elucidated. In this study, we investigated the effects of pirfenidone on proliferation, TGF-β-induced differentiation and fibrogenic activity of primary human lung fibroblasts (HLFs)...
July 16, 2014: European Journal of Pharmaceutical Sciences
Jing Wang, Yangfan Yang, Jiangang Xu, Xianchai Lin, Kaili Wu, Minbin Yu
PURPOSE: To investigate the effects of pirfenidone (PFD) on the migration, differentiation, and proliferation of retinal pigment epithelial (RPE) cells and demonstrate whether the drug induces cytotoxicity. METHODS: Human RPE cells (line D407) were treated with various concentrations of PFD. Cell migration was measured with scratch assay. The protein levels of fibronectin (FN), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), transforming growth factor beta (TGFβS), and Smads were assessed with western blot analyses...
2013: Molecular Vision
Xu Ji, Yukiko Naito, Huachun Weng, Xiao Ma, Kosuke Endo, Naoko Kito, Nariaki Yanagawa, Yang Yu, Jie Li, Naoharu Iwai
Pirfenidone (PFD) is a novel anti-fibrotic agent that targets TGFβ. However, the mechanisms underlying its renoprotective properties in hypertension-induced renal injury are poorly understood. We investigated the renoprotective properties of PFD and clarified its renoprotective mechanisms in a rat hypertension-induced renal injury model. Dahl salt-sensitive rats were fed a high-salt diet with or without 1% PFD for 6 weeks. During the administration period, we examined the effects of PFD on blood pressure and renal function...
2013: Biomedical Research
Zheng Xiao, Cheng-wen Li, Juan Shan, Lei Luo, Li Feng, Jun Lu, Sheng-fu Li, Dan Long, You-ping Li
OBJECTIVE: To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions in renal cell apoptosis. DATA SOURCES: We collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality, extracted data following PICOS principles and synthesized the data...
2013: Chinese Medical Journal
Kyoung In Jung, Jun-Sub Choi, Hyun Kyung Kim, Sun Young Shin
PURPOSE: To evaluate the usefulness of an anti-transforming growth factor-β (TGF-β) agent, pirfenidone (PFD) on postoperative inflammation and fibrosis following strabismus surgery in rabbits. METHODS: Both eyes of 16 New Zealand white rabbits underwent reinsertion of the superior rectus muscle (SRM). After reinsertion of the SRM, PFD-loaded liposomes (0.5 mg/ml) were injected into the right eye (PFD group) and normal saline-loaded liposomes was injected into the left eye (control group), subconjunctivally (0...
September 2012: Current Eye Research
Jean-Jacques Boffa, Jean-Claude Dussaule, Pierre Ronco, Christos Chatziantoniou
Despite the use of angiotensin blockers, chronic kidney diseases still progress. New therapeutic approaches aim to strengthen and to complete angiotensin blocker effects. Endothelin receptor antagonists, in addition to angiotensin blockers reduce blood pressure and urinary albumin excretion in diabetic nephropathies but can induce fluid overload. A second therapeutic approach consists in preventing the development of interstitial renal fibrosis which is a prognostic factor of CKD. Transforming growth factor-beta (TGF-beta) plays a major role in this process...
January 2012: La Revue du Praticien
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