Search results for "Translation"

Investigation of cancer drug resistance mechanisms by phosphoproteomics

2020

Abstract Cancer cell mutations can be identified by genomic and transcriptomic techniques. However, they are not sufficient to understand the full complexity of cancer heterogeneity. Analyses of proteins expressed in cancers and their modification profiles show how these mutations could be translated at the functional level. Protein phosphorylation is a major post-translational modification critical for regulating several cellular functions. The covalent addition of phosphate groups to serine, threonine, and tyrosine is catalyzed by protein kinases. Over the past years, kinases were strongly associated with cancer, thus inhibition of protein kinases emanated as novel cancer treatment. Howev…

In Situ Detection of Phosphorylated Platelet-derived Growth Factor Receptor β Using a Generalized Proximity Ligation Method

2007

Improved methods are needed for in situ characterization of post-translational modifications in cell lines and tissues. For example, it is desirable to monitor the phosphorylation status of individual receptor tyrosine kinases in samples from human tumors treated with inhibitors to evaluate therapeutic responses. Unfortunately the leading methods for observing the dynamics of tissue post-translational modifications in situ, immunohistochemistry and immunofluorescence, exhibit limited sensitivity and selectivity. Proximity ligation assay is a novel method that offers improved selectivity through the requirement of dual recognition and increased sensitivity by including DNA amplification as a…

Phosphorylation of Elp1 by Hrr25 is required for elongator-dependent tRNA modification in yeast.

2014

Elongator is a conserved protein complex comprising six different polypeptides that has been ascribed a wide range of functions, but which is now known to be required for modification of uridine residues in the wobble position of a subset of tRNAs in yeast, plants, worms and mammals. In previous work, we showed that Elongator's largest subunit (Elp1; also known as Iki3) was phosphorylated and implicated the yeast casein kinase I Hrr25 in Elongator function. Here we report identification of nine in vivo phosphorylation sites within Elp1 and show that four of these, clustered close to the Elp1 C-terminus and adjacent to a region that binds tRNA, are important for Elongator's tRNA modification…

P2‐307: A stable G‐quadruplex within the ADAM10 5'‐UTR is involved in translational repression of ADAM10

2011

Hypoxia-induced dysfunction of rat diaphragm

2004

Contains fulltext : 47331.pdf (Publisher’s version ) (Closed access) Oxidants may play a role in hypoxia-induced respiratory muscle dysfunction. In the present study we hypothesized that hypoxia-induced impairment in diaphragm contractility is associated with elevated peroxynitrite generation. In addition, we hypothesized that strenuous contractility of the diaphragm increases peroxynitrite formation. In vitro force-frequency relationship, isotonic fatigability, and nitrotyrosine levels were assessed under hypoxic (Po(2) approximately 6.5 kPa) and hyperoxic (Po(2) approximately 88.2 kPa) control conditions and also in the presence of authentic peroxynitrite (60 min), ebselen (60 min), and t…

Phase II study of pemetrexed and cisplatin plus cetuximab followed by pemetrexed and cetuximab maintenance therapy in patients with advanced nonsquam…

2013

Abstract Objectives The aim was to determine if combined pemetrexed, cisplatin, and cetuximab was efficacious and safe as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC). Patients and methods In this single-arm, multicenter clinical trial, patients with Stage IIIB/IV nonsquamous NSCLC received first-line therapy consisting of pemetrexed (500mg/m 2 ) and cisplatin (75mg/m 2 ) on Day 1 (21-day cycles) plus weekly cetuximab (400mg/m 2 loading dose, then 250mg/m 2 ) for 4–6 cycles. Non-progressing patients received maintenance therapy consisting of pemetrexed and cetuximab as above until disease progression. All patients received vitamin supplementation, dexameth…

P1.05-013 Lung Tumorspheres as a Platform for Testing New Therapeutic Strategies in Non-Small Cell Lung Cancer

2017

Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases

2017

The European Respiratory Society (ERS) Research Seminar entitled “Pulmonary vascular endothelium: orchestra conductor in respiratory diseases - highlights from basic research to therapy” brought together international experts in dysfunctional pulmonary endothelium, from basic science to translational medicine, to discuss several important aspects in acute and chronic lung diseases. This review will briefly sum up the different topics of discussion from this meeting which was held in Paris, France on October 27–28, 2016. It is important to consider that this paper does not address all aspects of endothelial dysfunction but focuses on specific themes such as: 1) the complex role of the pulmon…

Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure.

2017

Objectives Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. Methods IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth fa…

News from the Underground: What were the most important scientific/clinical take-home messages for juniors?

2014

The ERS International Congress has traditionally been a splendid opportunity to present current updates in clinical respiratory medicine and new research findings. This year’s programme was packed, making it impossible to attend all sessions, but juniors interested in specific fields were there for you to highlight the most important take home messages from the 2014 ERS International Congress in Munich. Amongst the most important news for the clinicians was the publication of a Global Initiative for Asthma (GINA) guidelines update [1]. In the updated guidelines, the heterogeneity of asthma is emphasised, suggesting the need of “4P” (Personalised, Predictive, Preventive and Participatory) tr…