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https://www.readbyqxmd.com/read/28806504/designing-liposomes-to-suppress-extracellular-matrix-expression-to-enhance-drug-penetration-and-pancreatic-tumor-therapy
#1
Tianjiao Ji, Jiayan Lang, Jing Wang, Rong Cai, Yinlong Zhang, Feifei Qi, Lijing Zhang, Xiao Zhao, Wenjing Wu, Jihui Hao, Zhihai Qin, Ying Zhao, Guangjun Nie
During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via co-assembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids...
August 14, 2017: ACS Nano
https://www.readbyqxmd.com/read/28790280/-perioperative-management-of-patients-with-pulmonary-comorbidities-undergoing-lung-resection
#2
Sumiko Maeda
Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) are 2 major pulmonary comorbidities of primary lung cancer patients. The COPD patients are at risk for respiratory failure after a major lung resection when lung resection exceeds the patient's pulmonary reserve. It is important to assess a postoperative risk based on the patient's cardiopulmonary function. Cardiac risks are initially evaluated for all the candidates for lung resection, then, ppoFEV1% and ppoDLco% are calculated...
July 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28780989/idiopathic-pleuroparenchymal-fibroelastosis-ppfe-a-case-study-of-a-rare-entity
#3
E B Boerner, U Costabel, T E Wessendorf, D Theegarten, F Bonella
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) was recognized as a rare new entity. We report the case of a 63 years old female suffering from progressive dyspnea and dry cough for three years. Two years before admission to our hospital, idiopathic pulmonary fibrosis (IPF) was diagnosed in another hospital and treatment with prednisolone and N-acetylcysteine (NAC) was commenced. At admission HRCT showed upper lobe dominant fibrosis and associated pleural thickening. Surgical biopsies were re-evaluated and revealed fibroelastosis with pleural thickening and a probable UIP pattern, consistent with idiopathic PPFE...
August 3, 2017: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/28774636/sleep-as-a-new-target-for-improving-outcomes-in-idiopathic-pulmonary-fibrosis-ipf
#4
REVIEW
Charalampos Mermigkis, Izolde Bouloukaki, Sophia E Schiza
Idiopathic pulmonary fibrosis (IPF) represents the most common type of interstitial pneumonias but remains a disease with a poor outcome. In recent years, two drugs (pirfenidone and nintedanib) have shown promising results at stalling disease progression, however, the interplay of sleep disruption or sleep disorders overall and in relation to medication effectiveness remains understudied. In the past, there was limited interest related to the role of sleep in IPF. Treating physicians tended to point only on the daily disabling symptoms disregarding the possible significant role of sleep alterations or co-existing sleep disorders...
July 31, 2017: Chest
https://www.readbyqxmd.com/read/28771451/pitfalls-in-developing-new-compounds-for-idiopathic-pulmonary-fibrosis
#5
Steven D Nathan, Fernando J Martinez
PURPOSE OF REVIEW: The development and availability of nintedanib and pirfenidone has heralded a new era in the management of idiopathic pulmonary fibrosis (IPF). Both agents demonstrate that the disease can be successfully modulated with therapeutic interventions, but neither are a cure and IPF remains a deadly disease. RECENT FINDINGS: There have been many lessons about the natural history of IPF and clinical trial design, not only from the clinical development programs for nintedanib and pirfenidone, but also the numerous negative trials that predated these...
September 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#6
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
https://www.readbyqxmd.com/read/28739874/the-k-ras-effector-p38p38%C3%AE-mapk-confers-intrinsic-resistance-to-tyrosine-kinase-inhibitors-by-stimulating-egfr-transcription-and-egfr-de-phosphorylation
#7
Ning Yin, Adrienne Lepp, Yongsheng Ji, Matthew Mortensen, Songwang Hou, Xiao-Mei Qi, Charles R Myers, Guan Guan
Mutations in K-Ras and epidermal growth factor receptor (EGFR) are mutually exclusive, but it is not known how K-Ras activation inactivates EGFR leading to resistance of cancer cells to anti-EGFR therapy. Here, we report that the K-Ras effector p38γMAPK confers intrinsic resistance to small molecular tyrosine kinase inhibitors (TKIs) by concurrently stimulating EGFR gene transcription and protein de-phosphorylation. We found that p38γ increases EGFR transcription by c-Jun mediated promoter-binding and stimulates EGFR de-phosphorylation via activation of protein tyrosine phosphatase H1 (PTPH1)...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28736462/sequential-release-of-multiple-drugs-from-flexible-drug-delivery-films
#8
Cheryl L Jennings, Ellis K Perry, Thomas D Dziubla, David A Puleo
Sequential release of drugs aligned with the phases of tissue healing could reduce scarring. To achieve this aim, layered film devices comprising cellulose acetate phthalate (CAP) and Pluronic F-127 (Pluronic) were loaded with ketoprofen, quercetin, and pirfenidone. Citrate plasticizers were added to impart flexibility. Release of two or three drugs in sequence over several days was obtained for all multilayered devices tested. Mechanical analysis showed that elongation increased and modulus decreased with increasing plasticizer content...
2017: International Journal of Polymeric Materials
https://www.readbyqxmd.com/read/28734935/outcome-of-lung-transplantation-in-idiopathic-pulmonary-fibrosis-with-previous-anti-fibrotic-therapy
#9
Gabriela Leuschner, Florian Stocker, Tobias Veit, Nikolaus Kneidinger, Hauke Winter, René Schramm, Thomas Weig, Sandhya Matthes, Felix Ceelen, Paola Arnold, Dieter Munker, Friederike Klenner, Rudolf Hatz, Marion Frankenberger, Jürgen Behr, Claus Neurohr
BACKGROUND: Anti-fibrotic drugs may interfere with wound-healing after major surgery, theoretically preventing sufficient bronchial anastomosis formation after lung transplantation (LTx). The aim of this study was to assess the impact of previous treatment with pirfenidone and nintedanib on outcomes after LTx in patients with idiopathic pulmonary fibrosis (IPF). METHODS: All patients with IPF undergoing LTx at the University of Munich between January 2012 and November 2016 were retrospectively screened for previous use of anti-fibrotics...
July 5, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28732832/current-approaches-to-the-management-of-idiopathic-pulmonary-fibrosis
#10
REVIEW
Ganesh Raghu, Luca Richeldi
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims of patient care are to improve outcomes for patients by slowing the progression of the disease, extending life, and improving quality of life. A prompt, accurate diagnosis is important to enable patients to receive treatment early in the course of the disease and to be considered for lung transplantation. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been shown to reduce decline in lung function in patients with IPF...
August 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28717083/pirfenidone-induced-eosinophilic-pleurisy
#11
Isano Hase, Bunpei Yamaguchi, Hidenori Takizawa, Hiroaki Arakawa, Hideo Sakuma, Koichi Fujiu, Hideaki Miyamoto, Yoshiki Ishii
The patient was a 69-year-old man with idiopathic pulmonary fibrosis who was taking pirfenidone. After 7 weeks of treatment, he suffered from left-sided eosinophilic pleurisy. Medical thoracoscopy was performed and the histopathological examination of the parietal pleura revealed the massive infiltration of eosinophils and lymphoid follicles. After stopping pirfenidone therapy, the patient's pleural effusion disappeared without additional treatment, and never recurred. This is the first case report of pirfenidone-induced pleurisy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28701252/idiopathic-pulmonary-fibrosis-a-case-discussion
#12
Meghan K Felton, Brian Bautista, Lee E Morrow, Mark Malesker
OBJECTIVE: The purpose of this report is to describe the case of a 68-year-old man who was treated for idiopathic pulmonary fibrosis (IPF), a chronic and fatal lung disease that is characterized by progressive deterioration of pulmonary function. He was initially prescribed pirfenidone and developed significant gastric distress. The treatment was transitioned to nintedanib. This article will provide the pharmacist with a therapeutic overview of IPF, as well as review the unique process involved with drug acquisition, dosing, patient education, and monitoring of pirfenidone and nintedanib...
July 1, 2017: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28699195/model-based-meta-analysis-on-the-efficacy-of-pharmacological-treatments-for-idiopathic-pulmonary-fibrosis
#13
Phyllis Chan, Leon Bax, Chunlin Chen, Nancy Zhang, Shu-Pang Huang, Holly Soares, Glenn Rosen, Malaz AbuTarif
Recently the FDA approved the first two drugs (pirfenidone and nintedanib) indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The purpose of this analysis was to leverage publicly available data to quantify comparative efficacy of compounds that are approved or in development. An analysis-ready database was developed, and the analysis dataset is composed of summary-level data from 43 arms in 20 trials, with treatment durations ranging from 8 to 104 weeks. A hierarchical multivariable regression model with non-parametric placebo estimation was used to fit the longitudinal profile of change from baseline of percent predicted forced vital capacity (%predicted FVC) data...
July 11, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28696894/preference-of-aerosolized-pirfenidone-to-oral-intake-an-experimental-model-of-pulmonary-fibrosis-by-paraquat
#14
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...
July 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28693256/pirfenidone-may-revert-the-epithelial-to-mesenchymal-transition-in-human-lung-adenocarcinoma
#15
Ryota Kurimoto, Takahiro Ebata, Shunichiro Iwasawa, Tsukasa Ishiwata, Yuji Tada, Koichiro Tatsumi, Yuichi Takiguchi
The epithelial-to-mesenchymal transition (EMT) in cancer is associated with invasion, metastasis and chemoresistance. Recent studies have revealed the increased expression of programmed death-ligand 1 (PD-L1) in cells undergoing EMT. The underlying mechanism of EMT involves transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2). Pirfenidone and the known EMT-suppressor nintedanib suppress pulmonary fibrosis partially through suppression of TGF-β. The present study aimed to determine whether pirfenidone has the potential to induce EMT-reversion, using nintedanib as a reference...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28688881/the-abdominal-skin-of-female-sprague-dawley-rats-is-more-sensitive-than-the-back-skin-to-drug-induced-phototoxicity
#16
Kazuhiro Kuga, Hironobu Yasuno, Yumi Sakai, Yumiko Harada, Fumi Shimizu, Yumiko Miyamoto, Yuki Takamatsu, Makoto Miyamoto, Keiichiro Sato
In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm(2) ultraviolet A...
July 5, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28688290/the-efficacy-of-plant-extract-and-bioactive-compounds-approaches-in-the-treatment-of-pulmonary-fibrosis-a-systematic-review
#17
REVIEW
Sana Bahri, Ridha Ben Ali, Anouar Abidi, Saloua Jameleddine
Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease leading to interstitial lung damage and serious breathing problems. The pathogenic mechanism involves activation, migration, proliferation and differentiation of fibroblasts into myofibroblats inducing extracellular matrix accumulation that destroy lung parenchyma. Available antifibrotic treatment options are limited to Pirfenidone and Nintedanib that prevent deterioration without an improvement of this disease. The use of plant extracts and natural bioactive compounds for the treatment of PF has been known for more than thirty years in China...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28674350/depression-is-significantly-associated-with-the-health-status-in-patients-with-idiopathic-pulmonary-fibrosis
#18
Toshiaki Matsuda, Hiroyuki Taniguchi, Masahiko Ando, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Koichi Nishimura, Osamu Nishiyama, Koji Sakamoto, Yoshinori Hasegawa
Objective Depression is reported to be relatively common in idiopathic pulmonary fibrosis (IPF) patients. Thus far, however, whether or not depression independently determines the health-related quality of life (HRQOL) has not been evaluated exclusively in IPF patients. We designed this study to identify independent determinants of the St. George' s Respiratory Questionnaire (SGRQ) score among various factors, including a depression scale, in IPF patients. Methods We retrospectively analyzed consecutive subjects with IPF who completed a systematic evaluation including pulmonary function tests, PaO2 at rest, 6-minute walk test (6MWT), SGRQ, Baseline Dyspnea Index (BDI), and Hospital Anxiety and Depression Scale (HADS)...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28668400/idiopathic-pulmonary-fibrosis-in-the-era-of-antifibrotic-therapy-searching-for-new-opportunities-grounded-in-evidence
#19
C Robalo-Cordeiro, P Campos, L Carvalho, A Borba, S Clemente, S Freitas, S Furtado, J M Jesus, C Leal, A Marques, N Melo, C Souto-Moura, S Neves, V Sousa, A Santos, A Morais
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that up to now has been associated with a poor prognosis. However, the results of the INPULSIS and ASCEND trials and the approval of nintedanib and pirfenidone have marked the beginning of a new era for IPF patients. Questions remain, however. Should these drugs be used earlier? What effect will they have on more severe disease? Will their effects last beyond the trial period? This manuscript is the outcome of a multidisciplinary meeting between pulmonology, radiology, and pathology clinicians on the use of antifibrotic agents in IPF...
June 28, 2017: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/28667654/idiopathic-pulmonary-fibrosis-ipf-common-practice-in-poland-before-the-antifibrotic-drugs-era
#20
Wojciech Jerzy Piotrowski, Magdalena M Martusewicz-Boros, Adam J Białas, Katarzyna Lewandowska
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and debilitating lung disease with a median survival time of 3-5 years. For now, pirfenidone (PIR) and nintedanib (NTB) are the only drugs that can slow down the disease's progression. In Poland, these drugs, although registered for legal use, had not been reimbursed for IPF patients until the end of the year 2016. Aim of the study was to assess what was common practice in terms of diagnosis and treatment in the period before antifibrotic drugs became available for IPF patients in Poland...
2017: Advances in Respiratory Medicine
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