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Nintedanib

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https://www.readbyqxmd.com/read/28798401/the-tyrosine-kinase-inhibitor-nintedanib-activates-shp-1-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#1
Chun-Yu Liu, Tzu-Ting Huang, Pei-Yi Chu, Chun-Teng Huang, Chia-Han Lee, Wan-Lun Wang, Ka-Yi Lau, Wen-Chun Tsai, Tzu-I Chao, Jung-Chen Su, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein...
August 11, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28774636/sleep-as-a-new-target-for-improving-outcomes-in-idiopathic-pulmonary-fibrosis-ipf
#2
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/28774597/nintedanib-reduces-radiation-induced-microscopic-lung-fibrosis-but-this-cannot-be-monitored-by-ct-imaging-a-preclinical-study-with-a-high-precision-image-guided-irradiator
#3
Dirk De Ruysscher, Patrick Vincent Granton, Natasja Gaby Lieuwes, Stefan van Hoof, Lutz Wollin, Birgit Weynand, Anne-Marie Dingemans, Frank Verhaegen, Ludwig Dubois
BACKGROUND: Nintedanib has anti-fibrotic and anti-inflammatory activity and is approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to noninvasively assess the efficacy of nintedanib in a mouse model of partial lung irradiation to prevent radiation-induced lung damage (RILD). METHODS: 266 C57BL/6 adult male mice were irradiated with a single radiation dose (0, 4, 8, 12, 16 or 20Gy) using parallel-opposed fields targeting the upper right lung using a precision image-guided small animal irradiator sparing heart and spine based on micro-CT images...
July 31, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28772332/-expert-knowledge-and-supporting-advice-for-the-clinical-use-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#4
J Behr, A Günther, M Kreuter, D Koschel, A Prasse, M Pfeifer, U Costabel
In October 2016, a group of German IPF experts were invited by Boehringer Ingelheim to meet in Frankfurt with the aim, (a) to discuss relevant aspects of the management and treatment of idiopathic pulmonary fibrosis (IPF) using nintedanib; and, (b) to provide supportive advice for daily clinical practice with nintedanib. The resulting information compiled in this document is confined to practical issues regarding the use of nintedanib in patients with IPF. Where different therapeutic options were available, the choice of IPF medication was not discussed and the experts alluded to current guidelines for the diagnosis and treatment of IPF...
August 3, 2017: Pneumologie
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/28761724/time-since-start-of-first-line-therapy-as-a-predictive-clinical-marker-for-nintedanib-in-patients-with-previously-treated-non-small-cell-lung-cancer
#6
Birgit Gaschler-Markefski, Patricia Sikken, John V Heymach, Maya Gottfried, Anders Mellemgaard, Silvia Novello, Claudia-Nanette Gann, José Barrueco, Martin Reck, Nasser H Hanna, Rolf Kaiser
INTRODUCTION: No predictive clinical or genetic markers have been identified or validated for antiangiogenic agents in lung cancer. We aimed to identify a predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor, using data from two large second-line non-small cell lung cancer Phase III trials (LUME-Lung 1 ([LL1] and LUME-Lung 2). METHODS: Predictive marker identification was conducted in a multi-step process using data from both trials; a hypothesis was generated, confirmed and validated...
2017: ESMO Open
https://www.readbyqxmd.com/read/28751539/mechanisms-of-resistance-to-ntrk-inhibitors-and-therapeutic-strategies-in-ntrk1-rearranged-cancers
#7
Miho J Fuse, Koutaroh Okada, Tomoko Oh-Hara, Hayato Ogura, Naoya Fujita, Ryohei Katayama
Neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangement leads to constitutive activation of NTRK1, which induces high transforming ability. NTRK-rearranged cancers have been identified in several cancer types, such as glioblastoma, non-small-cell lung cancer, and colorectal cancer. Although there are currently no clinically approved inhibitors that target NTRK1, several tyrosine kinase inhibitors (TKIs), such as entrectinib and LOXO-101, are in clinical trials. The purpose of this study was to identify potential mechanisms of resistance to NTRK inhibitors and find potential therapeutic strategies to overcome the resistance...
July 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28734935/outcome-of-lung-transplantation-in-idiopathic-pulmonary-fibrosis-with-previous-anti-fibrotic-therapy
#8
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
#9
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/28721753/nintedanib-in-ovarian-cancer
#10
Saira Khalique, Susana Banerjee
Advanced ovarian cancer remains an unmet clinical need. Angiogenesis is considered a therapeutic target in ovarian cancer, with bevacizumab, a monoclonal antibody against VEGF, being the first drug to show a progression-free survival benefit. Nintedanib is an oral tyrosine kinase inhibitor targeting VEGF receptor 1-3, FGFR 1-3 and PDGFR α and β, which has entered phase III trial development in ovarian cancer. Areas covered: This article reviews the preclinical and clinical efficacy of nintedanib in ovarian cancer, its pharmacokinetic and pharmacodynamics profile, safety issues, together with an overview of clinical trials carried out so far...
July 19, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28714017/targeting-vegfr-and-fgfr-in-head-and-neck-squamous-cell-carcinoma-in-vitro
#11
Roman C Brands, Luise M Knierim, Francesco De Donno, Valentin Steinacker, Stefan Hartmann, Axel Seher, Alexander C Kübler, Urs D A Müller-Richter
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by a tumor microenvironment (TME) that overexpresses vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which can lead to neovascularization, tumor growth and metastasis. Therapeutic strategies inhibiting these signaling pathways might lead to innovative HNSCC treatments. Five HNSCC cell lines were characterized based on VEGFR1-3 and FGFR1-4 expression by sqRT-PCR and treated with three different tyrosine kinase inhibitors (TKIs) (nintedanib, dovitinib and pazopanib), all of which are effective against VEGFR and FGFR family members...
July 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28702806/efficacy-and-safety-of-nintedanib-plus-docetaxel-in-patients-with-advanced-lung-adenocarcinoma-complementary-and-exploratory-analyses-of-the-phase-iii-lume-lung-1-study
#12
Maya Gottfried, Jaafar Bennouna, Igor Bondarenko, Jean-Yves Douillard, David F Heigener, Maciej Krzakowski, Anders Mellemgaard, Silvia Novello, Sergei Orlov, Yvonne Summers, Joachim von Pawel, Julia Stöhr, Rolf Kaiser, Martin Reck
BACKGROUND: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months. OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT...
August 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28701252/idiopathic-pulmonary-fibrosis-a-case-discussion
#13
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
#14
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/28696800/effect-of-nintedanib-on-airway-inflammation-and-remodeling-in-a-murine-chronic-asthma-model
#15
Hwa Young Lee, Jung Hur, In Kyoung Kim, Ji Young Kang, Hyoung Kyu Yoon, Sook Young Lee, Soon Suk Kwon, Young Kyoon Kim, Chin Kook Rhee
INTRODUCTION: Nintedanib is a multi-tyrosine kinase receptor inhibitor recently approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is a key process involved in airway structural changes in patients with bronchial asthma, the effect of nintedanib targeting the angiokinase pathway on airway inflammation and remodeling has not been evaluated. METHODS: We used a 3-month ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally administrated during the challenge period, and the effects were examined based on the percentage of airway inflammatory cells, airway hyper-reactivity (AHR), peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle area...
July 11, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28693256/pirfenidone-may-revert-the-epithelial-to-mesenchymal-transition-in-human-lung-adenocarcinoma
#16
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/28690011/lume-meso-design-and-rationale-of-the-phase-iii-part-of-a-placebo-controlled-study-of-nintedanib-and-pemetrexed-cisplatin-followed-by-maintenance-nintedanib-in-patients-with-unresectable-malignant-pleural-mesothelioma
#17
Giorgio V Scagliotti, Rabab Gaafar, Anna K Nowak, Martin Reck, Anne S Tsao, Jan van Meerbeeck, Nicholas J Vogelzang, Takashi Nakano, Ute von Wangenheim, Derek Velema, Nassim Morsli, Sanjay Popat
Malignant pleural mesothelioma (MPM) is a rare but aggressive disease: median survival is 6 to 9 months if untreated. Standard first-line treatment for patients with unresectable MPM is cisplatin/pemetrexed, with a median overall survival (OS) of approximately 1 year. Improvements in first-line treatment options are needed. With the benefit of combining bevacizumab with standard therapy shown in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS), vascular endothelial growth factor (VEGF) pathway inhibition has gained renewed interest as a treatment approach...
March 22, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28688290/the-efficacy-of-plant-extract-and-bioactive-compounds-approaches-in-the-treatment-of-pulmonary-fibrosis-a-systematic-review
#18
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/28687482/treatment-rationale-and-design-for-j-sonic-a%C3%A2-randomized-study-of-carboplatin-plus-nab-paclitaxel-with-or-without-nintedanib-for-advanced-non-small-cell-lung-cancer-with-idiopathic-pulmonary-fibrosis
#19
Kohei Otsubo, Junji Kishimoto, Hirotsugu Kenmotsu, Yuji Minegishi, Eiki Ichihara, Akira Shiraki, Terufumi Kato, Shinji Atagi, Hidehito Horinouchi, Masahiko Ando, Yasuhiro Kondoh, Masahiko Kusumoto, Kazuya Ichikado, Nobuyuki Yamamoto, Yoichi Nakanishi, Isamu Okamoto
We describe the treatment rationale and procedure for a randomized study (J-SONIC; University Hospital Medical Information Network Clinical Trials Registry identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The study was designed to examine the efficacy and safety of nintedanib administered with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone in chemotherapy-naive patients with advanced NSCLC associated with IPF...
June 20, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28668400/idiopathic-pulmonary-fibrosis-in-the-era-of-antifibrotic-therapy-searching-for-new-opportunities-grounded-in-evidence
#20
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
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