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showing 10 items of 3120 documents
The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis
2018
Abstract Introduction Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. Patients and Methods Clinical trials were selected by searching “Pubmed” database and abstracts from major cancer meetings. We considered the January 2008 - April 2018 time frame. Progression free surv…
Monitoring blood biomarkers to predict nivolumab effectiveness in NSCLC patients
2019
Background: We investigated whether early dynamic changes of circulating free (cfDNA) levels as well as the neutrophil to lymphocyte ratio (NLR) could predict nivolumab effectiveness in pretreated patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 45 patients receiving nivolumab 3 mg/kg every 2 weeks were enrolled. Patients underwent a computed tomography scan and responses were evaluated by the response evaluation criteria in solid tumors. Peripheral blood samples were obtained from the patients and the cfDNA level as well as the NLR were assessed. Time to progression (TTP) and overall survival (OS) were determined. Results: Patients with increased cfDNA >20%…
Is ovarian cancer a targetable disease? A systematic review and meta-analysis and genomic data investigation
2016
// Nicoletta Staropoli 1, * , Domenico Ciliberto 1, * , Silvia Chiellino 1 , Francesca Caglioti 1 , Teresa Del Giudice 1 , Simona Gualtieri 1 , Angela Salvino 1 , Alessandra Strangio 1 , Cirino Botta 1 , Sandro Pignata 2 , Pierfrancesco Tassone 1, * , Pierosandro Tagliaferri 1, * 1 Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy 2 Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples, Naples, Italy * These authors have contributed equally to this work Correspondence to: Pierosandro Tagliaferri, email: tagliaferri@unicz.it Keywords: ovarian cancer, targeted therapy, systemic chemotherapy, systemat…
Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer
2018
Giuseppe Cicero,1 Rossella De Luca,1 Francesco Dieli2 1Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; 2Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy Background: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. Methods: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hu…
Non-invasive Biomarkers of Acute Rejection in Kidney Transplantation: Novel Targets and Strategies
2019
Abstract: Kidney transplantation is considered the favored treatment for patients suffering from end-stage renal disease, since successful transplantation is associated with longer survival and improved quality of life compared to dialysis. Alloreactive immune responses against the donor kidney may lead to acute rejection of the transplant. The current diagnosis of renal allograft rejection mainly relies on clinical monitoring, including serum creatinine, proteinuria, and confirmation by histopathologic assessment in the kidney transplant biopsy. These parameters have their limitations. Identification and validation of biomarkers, which correlate with or predict the presence of acute reject…
Models of cortical malformation--Chemical and physical.
2015
Abstract Pharmaco-resistant epilepsies, and also some neuropsychiatric disorders, are often associated with malformations in hippocampal and neocortical structures. The mechanisms leading to these cortical malformations causing an imbalance between the excitatory and inhibitory system are largely unknown. Animal models using chemical or physical manipulations reproduce different human pathologies by interfering with cell generation and neuronal migration. The model of in utero injection of methylazoxymethanol (MAM) acetate mimics periventricular nodular heterotopia. The freeze lesion model reproduces (poly)microgyria, focal heterotopia and schizencephaly. The in utero irradiation model caus…
Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells.
2016
Background & Aims Wheat amylase-trypsin inhibitors (ATIs) are nutritional activators of innate immunity, via activation of the toll-like receptor 4 (TLR4) on myeloid cells. We aimed to characterize the biologic activity of ATIs in various foods and their effect on intestinal inflammation. Methods We selected 38 different gluten-containing and gluten-free products, either unprocessed (such as wheat, rye, barley, quinoa, amaranth, soya, lentils, and rice) or processed (such as pizza, pasta, bread, and biscuits). ATIs were extracted and their biological activities determined in TLR4-responsive mouse and human cell lines. Effects of oral ATIs on intestinal inflammation were determined in health…
Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein
2016
Many biological processes depend on detecting and responding to light. The response is often mediated by a structural change in a protein that begins when absorption of a photon causes isomerization of a chromophore bound to the protein. Pande et al. used x-ray pulses emitted by a free electron laser source to conduct time-resolved serial femtosecond crystallography in the time range of 100 fs to 3 ms. This allowed for the real-time tracking of the trans-cis isomerization of the chromophore in photoactive yellow protein and the associated structural changes in the protein.Science, this issue p. 725A variety of organisms have evolved mechanisms to detect and respond to light, in which the re…
Coarse-grained models of double-stranded DNA based on experimentally determined knotting probabilities
2018
Abstract To accurately model double-stranded DNA in a manner that is computationally efficient, coarse-grained models of DNA are introduced, where model parameters are selected by fitting the spectrum of observable DNA knots: We develop a general method to fit free parameters of coarse-grained chain models by comparing experimentally obtained knotting probabilities of short DNA chains to knotting probabilities that are computed in Monte Carlo simulations, resulting in coarse-grained DNA models which are tailored to reflect DNA topology in the best possible way. The method is exemplified by fitting ideal chain models as well as a bead-spring model with excluded volume interactions, to model …
Entropic Interactions between Two Knots on a Semiflexible Polymer.
2017
Two knots on a string can either be separated or intertwined, and may even pass through each other. At the microscopic scale, such transitions may occur spontaneously, driven by thermal fluctuations, and can be associated with a topological free energy barrier. In this manuscript, we study the respective location of a trefoil ( 3 1 ) and a figure-eight ( 4 1 ) knot on a semiflexible polymer, which is parameterized to model dsDNA in physiological conditions. Two cases are considered: first, end monomers are grafted to two confining walls of varying distance. Free energy profiles and transition barriers are then compared to a subset of free chains, which contain exactly one 3 1 and one 4 1 kn…