Search results for "GFR"

Age-dependent regulation of antioxidant genes by p38α MAPK in the liver

2018

p38α is a redox sensitive MAPK activated by pro-inflammatory cytokines and environmental, genotoxic and endoplasmic reticulum stresses. The aim of this work was to assess whether p38α controls the antioxidant defense in the liver, and if so, to elucidate the mechanism(s) involved and the age-related changes. For this purpose, we used liver-specific p38α-deficient mice at two different ages: young-mice (4 months-old) and old-mice (24 months-old). The liver of young p38α knock-out mice exhibited a decrease in GSH levels and an increase in GSSG/GSH ratio and malondialdehyde levels. However, old mice deficient in p38α had higher hepatic GSH levels and lower GSSG/GSH ratio than young p38α knock-…

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

2012

Abstract SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERα−positive MCF-7 and the ERα−negative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show…

Hitler A Bayreuth. Storia di un'amicizia (1923-1940)

2013

Il saggio si sofferma sulle vite parallele di Winifred Majorie Williams (moglie di Sigfried Wagner e dopo la sua morte "Signora di Bayreuth") e Adolf Hitler, grande ammiratore dell'opera wagneriana e "amico" di famiglia della famiglia Wagner a partire dalla fine degli anni Venti. Il testo ripercorre le tappe del rapporto personale fra Winifred Wagner e Adolf Hitler, rievocando al tempo stesso alcuni episodi della biografia hitleriana legati al Festival di Bayreuth.

Abstract LB-295: Detection of oncogenic kinase mutations in circulating plasma DNA and correlation with clinical benefit in the phase III GRID study …

2013

Abstract Background: GRID is a phase III study for patients with advanced gastrointestinal stromal tumors (GIST) following failure of imatinib (I) and sunitinib (S) who were randomized to receive either the multikinase inhibitor regorafenib (R) or placebo (P). R demonstrated a highly significant improvement in progression-free survival compared with P (HR 0.27, p<0.0001). A preplanned retrospective biomarker analysis was conducted to assess GIST genotypes in GRID patients and to explore the possible impact of different driver oncogene mutations on clinical outcomes. Methods: DNA was isolated from archival tumor tissue and analyzed for KIT mutations via Sanger sequencing. The expectat…

Progettazione e sintesi di nuovi complessi metallici potenziali inibitori di FGFR4

2019

I pathways di segnalazione che coinvolgono il recettore del fattore di crescita dei fibroblasti 4 (FGFR4) risultano alterati in varie tipologie di tumori [1] ed è stato dimostrato come l’interruzione della segnalazione FGF19/FGFR4 interrompa la proliferazione e induca l’apoptosi delle cellule tumorali, offrendo grandi promesse terapeutiche. [2-4] Allo scopo d’individuare nuovi leganti FGFR4, sono stati effettuati degli studi di modellistica molecolare (Fig. 1) che, riferendosi alla struttura del ponatinib, noto inibitore di FGFR4, [5] il cui utilizzo è ostacolato dall’elevata lipofilia e da effetti secondari, hanno consentito di generare una “Drug Discovery Library” di oltre 30 nuovi potenz…

Design of copper(II) complexes as potential anticancer prodrugs

The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in cell growth, survival, and migration as well as in maintaining tumor angiogenesis (1). FGFR genetic alterations are frequently observed in cancer, suggesting that FGFR inhibition may be a promising therapy in patients harboring these lesions (2). In particular, molecules with structural properties similar to Ponatinib, a known inhibitor of FGFR, that shows a selective interaction for the ATP binding site of the isoform 4 of these receptors (FGFR4), are being considered. Molecular modeling studies have been conducted to design novel po…

Experimental and numerical analysis of flexural behaviour of GFRP pultruded material

2014

Kracauer, Siegfried: Werke. Hrsg. von Inka Mülder-Bach und Ingrid Belke. – Frankfurt am Main: Suhrkamp. [Bd.] 4. Geschichte – Vor den letzten Dingen.…

2010

Recensione

RECHALLENGE WITH ANTI-EGFR MONOCLONAL ANTIBODIES IN PRETREATED METASTATIC COLORECTAL CANCER PATIENTS: BEYOND THE LIMITS OF ACQUIRED RESISTANCE

2012

Background: Scientific data provide today the evidence that secondary K-RAS mutations do not occur during anti-EGFR therapy in CRC patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and Methods: we enrolled 39 irinotecan refractory patients who had a clinical benefit after a line of Cetuximab plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were re-treated with the same Cetuximab plus Irinotecan based therapy. Results: Median number of therapeutic lines before accrual was 4. Median inte…

The role of microRNAs in driving EGFR-TKI resistance in NSCLC cell lines

2016

Background: the inhibition of EGFR kinase activity by tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, can result in improved response and prolonged progression-free survival (PFS) in NSCLC patients harboring sensitizing exon 19del and exon 21 L858R mutations. Unfortunately, almost all patients will develop resistance to EGFR-TKI, in particular T790M is the most frequent mutation. Nowadays, new methods are urgently needed for a rapid, cost-effective and non-invasive identification of biomarkers as a valuable tool for obtaining the genetic follow-up data during the course of the disease. Circulating microRNAs might represent a new precious biomarker for patients’ moni…