Search results for "GEF"
showing 10 items of 48 documents
Cytotoxicity of the bisphenolic honokiol from Magnolia officinalis against multiple drug-resistant tumor cells as determined by pharmacogenomics and …
2014
A main problem in oncology is the development of drug-resistance. Some plant-derived lignans are established in cancer therapy, e.g. the semisynthetic epipodophyllotoxins etoposide and teniposide. Their activity is, unfortunately, hampered by the ATP-binding cassette (ABC) efflux transporter, P-glycoprotein. Here, we investigated the bisphenolic honokiol derived from Magnolia officinalis. P-glycoprotein-overexpressing CEM/ADR5000 cells were not cross-resistant to honokiol, but MDA-MB-231 BRCP cells transfected with another ABC-transporter, BCRP, revealed 3-fold resistance. Further drug resistance mechanisms analyzed study was the tumor suppressor TP53 and the epidermal growth factor recepto…
The comparison of outcomes from tyrosine kinase inhibitor monotherapy in second- or third-line for advanced non-small-cell lung cancer patients with …
2016
// Giuseppe Bronte 1, * , Tindara Franchina 2, * , Massimiliano Alu 3, * , Giovanni Sortino 1 , Claudia Celesia 1 , Francesco Passiglia 1 , Giuseppina Savio 3 , Agata Laudani 3 , Alessandro Russo 2 , Antonio Picone 2 , Sergio Rizzo 1 , Michele De Tursi 4 , Elisabetta Gambale 4 , Viviana Bazan 1 , Clara Natoli 4 , Livio Blasi 3 , Vincenzo Adamo 2 , Antonio Russo 1 1 Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy 3 Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy 4 Department of Medical, Oral and Biotechnological …
Conserved role of Ras-GEFs in promoting aging: from yeast to mice
2011
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging, lifespan and metabolic parameters were analyzed in aged RasGrf1(-/-) mice. We observed that mice deficient for RasGrf1(-/-) display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals. Aged RasGrf1(-/-) displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1(-/-). IGF-I lev…
Benchmark of a multi-physics Monte Carlo simulation of an ionguide for neutron-induced fission products
2022
AbstractTo enhance the production of medium-heavy, neutron-rich nuclei, and to facilitate measurements of independent yields of neutron-induced fission, a proton-to-neutron converter and a dedicated ion guide for neutron-induced fission have been developed for the IGISOL facility at the University of Jyväskylä. The ion guide holds the fissionable targets, and the fission products emerging from the targets are collected in helium gas and transported to the downstream experimental stations. A computer model, based on a combination of MCNPX for modeling the neutron production, the fission code GEF, and GEANT4 for the transport of the fission products, was developed. The model will be used to i…
Third-line therapy for advanced non-small-cell lung cancer patients: a feasible therapeutic option?
2010
Two decades ago best supportive care was considered a valid therapeutic option for advanced non-small cell lung cancer (NSCLC) patients until the evidence derived from meta-analysis showed symptom improvement and a survival advantage from systemic chemotherapy. A further advantage was reported when docetaxel and pemetrexed were used as second-line treatment after failure of first-line platinum-based chemotherapy. Furthermore, the biologic therapies targeting the epidermal growth factor receptor – erlotinib and gefitinib – have modified the therapeutic approach to second- and third-line treatment of NSCLC patients. In fact, to date, erlotinib is the only drug to be licensed for third-line th…
Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with advanced EGFR-mutated non-small-cell lung cancer.
2021
To evaluate the cost-effectiveness of first-line treatments, such as erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib, for patients diagnosed with stage IIIB/IV NSCLC harboring EGFR mutations.A partitioned survival model was developed to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) from the perspective of the Spanish National Health System. Two Bayesian NMAs were performed independently, by using the polynomial fraction method to fit Kaplan-Meier curves for overall survival and progression-free survival. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty.The ICER was calculated for the fou…
Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clin…
2014
Abstract: Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comp…
Improvement in Lung Cancer Outcomes With Targeted Therapies: An Update for Family Physicians.
2015
Abstract: In the past decade the advent of target therapy has led to a silent revolution in the treatment of lung cancer. Thanks to the specificity of their target, new tailored drugs are able to achieve a larger benefit and lower toxicity and provide better quality of life than cytotoxic drugs in a limited number of patients, selected by molecular profile. Nowadays, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment of non-small-cell lung cancer. Family physicians play an important role in the treatment, detection, and management of common toxicities and…
Adding chemotherapy to TKI: Can we improve first-line treatment for EGFR-mutated NSCLC patients?
2016
In The Journal of Clinical Oncology , Ying Cheng and colleagues (1) have recently reported the results of a phase II randomized trial comparing pemetrexed plus gefitinib vs. gefitinib in treatment-naive, East Asian patients, with advanced non-squamous non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations. The study met its primary end-point in the intent-to-treat population, showing a significantly longer median progression free survival (PFS) in favors of the combination arm (15.8 months) compared to single agent arm (10.9 months) [hazard ratio (HR): 0.68; 95% CI, 0.48 to 0.96; one-sided P=0.014; two-sided P=0.029].
Interstitial lung disease associated with drug therapy
2004
Drug-associated interstitial lung disease (ILD) is not uncommon, with diverse patterns ranging from benign infiltrates to the potentially fatal acute respiratory distress syndrome. As acute respiratory failure due to drug-associated ILD has an unpredictable onset and rapid time course, establishing a diagnosis is often difficult. An accurate diagnosis is based on clinical, radiological (including high-resolution computed tomography) and histological manifestations, although is often only possible by exclusion. Cancer chemotherapy is commonly associated with acute disease that, on pathology, is often diffuse alveolar damage. Furthermore, a combination of drugs with or without radiotherapy ca…