Search results for "FGF"

Design, synthesis and biological evaluation of new anticancer drugs: FGFR inhibitors

2021

Fibroblast growth factor receptors (FGFRs) constitute a family of tyrosine kinases receptors (RTKs) that exert pivotal physiological functions in human embryonic and adult tissues. Hyperactivated FGFR signaling drives tumorigenesis in multiple cancer types, including lung and brain cancers. Great effort has been laid on the development of new compounds that specifically target the FGFR axis. However, cancer cell- based and microenvironmental resistance mechanisms against FGFR inhibitors often arise and are currently poorly understood. Furthermore, FGFR-targeted therapy often presents different side effects, e due to the broad biological spectrum of the FGFR signaling axis as well as to its …

Meccanismi non convenzionali di secrezione dell’FGF-2

2004

FGF-2/FGFR neurotrophic system expression level does not give account for the age-related decline of neurogenesis in the rat brain.

2009

Analysis of intracellular FGF-2 trafficking in Sk-Hep1 cells.

2005

Fibroblast Growth Factor-21 (FGF-21) enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons.

2014

FGF-21 è un fattore di crescita ad azione endocrina principalmente espresso nel fegato con funzioni metaboliche; induce a livello epatico e in altri tessuti incremento di PGC1, ma le sue funzioni a livello cerebrale sono ancora sconosciute. PGC1 è espresso anche nel cervello dove mostra azione neuroprotettiva in neuroni dopaminergici in modelli animali di morbo di Parkinson. Scopo della ricerca era indagare possibili correlazioni tra le due proteine a livello cerebrale. I dati mostrano che FGF-21 induce attivazione di PGC1 mediante la deacetilasi Sirtuina-1 NAD+ dipendente, in neuroni dopaminergici e un incremento dell’attività respiratoria mitocondriale. FGF-21 risulta espresso nel cerv…

Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus.

2021

This article also appears in: Health, Medical, and Life Sciences Virtual Issue for Advanced Science.

Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1

2014

Abstract Mitochondrial dysfunctions accompany several neurodegenerative disorders and contribute to disease pathogenesis among others in Parkinson’s disease (PD). Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a major regulator of mitochondrial functions and biogenesis, and was suggested as a therapeutic target in PD. PGC-1α is regulated by both transcriptional and posttranslational events involving also the action of growth factors. Fibroblast growth factor-21 (FGF21) is a regulator of glucose and fatty acid metabolism in the body but little is known about its action in the brain. We show here that FGF21 increased the levels and activity of PGC-1α and elevated mito…

Neuronal FGFR1 transactivation by inducing FGFR1/5-HT1A heteroreceptor complexes formation

2011

There are no clear data on the molecular mechanism by which the hippocampal 5-HT transmission contributes to the neuroprotective and antidepressant effects of 5-HT uptake blockers. Previously, we revealed that a 5-HT1A agonist may induce phosphorylation of FGFR1 and ERK1/2 in rat hippocampus independent of FGF-2, suggesting transactivation of FGFR1 tyrosine kinase in the absence of neurotrophic factor binding. As extension of previous work, using BRET analysis and coimmunoprecipitation in cellular models, FGFR1-5-HT1A heteroreceptor complexes have been demonstrated and agonist modulation characterized. In vitro assays on ERK1/2 phosphorylation in HEK cells and primary hippocampal cultures h…

The Co‐mutational Spectrum Determines the Therapeutic Response in Murine FGFR2 Fusion‐Driven Cholangiocarcinoma

2021

Background and aims Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and a highly lethal malignancy. Chemotherapeutic options are limited, but a considerable subset of patients harbors genetic lesions for which targeted agents exist. Fibroblast growth factor receptor 2 (FGFR2) fusions belong to the most frequent and therapeutically relevant alterations in ICC, and the first FGFR inhibitor was recently approved for the treatment of patients with progressed, fusion-positive ICC. Response rates of up to 35% indicate that FGFR-targeted therapies are beneficial in many but not all patients. Thus far, no established biomarkers exist that predict resistance or r…

Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-dr…

2017

Background Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. Methods 3-dimens…