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| 1 | Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer显示文摘The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(EGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-EGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them. | Vincenzo Sforza Erika Martinelli Fortunato Ciardiello Valentina Gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli Teresa Troiani | 2016 | World Journal of Gastroenterology2016，22，28： | 6 |
| 2 | A high-density, multi-parental SNP genetic map on apple validates a new mapping approach for outcrossing species显示文摘Quantitative trait loci(QTL)mapping approaches rely on the correct ordering of molecular markers along the chromosomes,which can be obtained from genetic linkage maps or a reference genome sequence.For apple(Malus domestica Borkh),the genome sequence v1 and v2 could not meet this need;therefore,a novel approach was devised to develop a dense genetic linkage map,providing the most reliable marker-loci order for the highest possible number of markers.The approach was based on four strategies:(i)the use of multiple full-sib families,(ii)the reduction of missing information through the use of HaploBlocks and alternative calling procedures for single-nucleotide polymorphism(SNP)markers,(iii)the construction of a single backcross-type data set including all families,and(iv)a two-step map generation procedure based on the sequential inclusion of markers.The map comprises 15417 SNP markers,clustered in 3 K HaploBlock markers spanning 1267 cM,with an average distance between adjacent markers of 0.37 cM and a maximum distance of 3.29 cM.Moreover,chromosome 5 was oriented according to its homoeologous chromosome 10.This map was useful to improve the apple genome sequence,design the Axiom Apple 480 K SNP array and perform multifamily-based QTL studies.Its collinearity with the genome sequences v1 and v3 are reported.To our knowledge,this is the shortest published SNP map in apple,while including the largest number of markers,families and individuals.This result validates our methodology,proving its value for the construction of integrated linkage maps for any outbreeding species. | Erica A Di Pierro Luca Gianfranceschi Mario Di Guardo Herma JJ Koehorst-van Putten Johannes W Kruisselbrink Sara Longhi Michela Troggio Luca Bianco Hélène Muranty Giulia Pagliarani Stefano Tartarini Thomas Letschka Lidia Lozano Luis Larisa Garkava-Gustavsson Diego Micheletti Marco CAM Bink Roeland E Voorrips Ebrahimi Aziz Riccardo Velasco François Laurens W Eric van de Weg | 2016 | Horticulture Research2016，3，1： | 3 |
| 3 | Female urinary incontinence during pregnancy and after delivery: Clinical impact and contributing factors显示文摘Urinary incontinence(UI) is a common condition affecting adult women of all ages and it could have a negative infl uence on quality of life. The etiology of UI is multifactorial, but some of the most important risk factors are obesity and ageing, as well as adverse obstetric events. Pregnancy and delivery per se have been implicated in the etiology of UI. Although several studies have demonstrated a direct association between UI and vaginal delivery in short, medium and long-term, the role of childbirth on the risk of UI remains controversial. The mechanical strain during delivery may induce injuries to the muscle, connective and neural structures. Vaginal birth can be associated with relaxation or disruption of fascial and ligamentous supports of pelvic organs. Parity, instrumental delivery, prolonged labor and increased birth weights have always been considered risk factors for pelvic floor injury. Also genetic factors have been recently raised up but still there are not appropriate guidelines or measures to reduce signifi cantly the incidence of UI. The role of pelvic fl oor muscle training(PFMT) in the prevention and treatment of UI is still unclear. However, PFMT seems to be useful when supervised training is conducted and it could be incorporated as a routine part of women's exercise programmes during pregnancy and after childbirth. | Paolo Mannella Giulia Palla Gonzalo Pérez-Roncero María T López-Baena Faustino R Pérez-López | 2013 | World Journal of Obstetrics and Gynecology2013，2，4： | 2 |
| 4 | Heart rate variability as an index of sympathovagal Interaction after acute myocardial Infarction显示文摘 | FEDRICO L O GIULIA S A SILVIA P E | 1987 | Am J Cardiol1987，60，： | 1 |
| 5 | Self- assembling and antioxidant activity of some vitamin C derivatives 显示文摘 | PIERANDREA L N GIULIA C PATRIZIA P | 2000 | Colloids and Surfaces A: Physicochemical and Engineering Aspects2000，，167： | 1 |
| 6 | p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive event in human glioblastoma显示文摘 | Giulia F Martin L Yan L | 2000 | Oncogene2000，19，： | 1 |
| 7 | Intraoperative parathyroid hormone assay during focused parathyroidectomy: the importance t显示文摘 | Pietro GO Giuseppe P Giulia L | 2013 | BMC Surg2013，13，： | 1 |
| 8 | Heart rate variability as an index of sympathovagal Interaction after acute myocardial Infarction显示文摘 | FEDRICO L O GIULIA S A SILVIA P E | 1987 | Am J Cardiol1987，60，： | 1 |
| 9 | An improvedfive-parameter model for photovoltaic modules 显示文摘 | Brano V L Orioli A Giulia G | 2010 | SolarEnergy Materials & Solar GeUs2010，94，8： | 1 |
| 10 | et al, Splenic CD4^+ and CD8^+ T cells from influenza immune mice concurrently produce in vitro IL2, IL4, and IFN-γ 显示文摘 | Roberto F Giulia L Ida A | 1996 | Cell Immunol1996，170，2： | 1 |
| 11 | Sorting out the roles PPAR-αin the energy metabolism and vascular homeostasis显示文摘 | PHILIPPE L GIULIA G JEAN-CHARIES F | | 0，，03： | 1 |
| 12 | Mycophenolate mofetil versus AZAthioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial显示文摘 | Giuseppe R Mariadomenica L Eliana G Maria G Borislav DD Bogdan EI Giulia G Donato D Maurizio S Silvio S Umberto V Giuseppe S Georges M Stefano F Paolo R Vito S Jean-Louis B Norberto P Piero R | 2004 | Lancet2004，364，7： | 1 |
| 13 | Superior vena cava resection for lung and mediastinal malignancies: a single-center experience with 70 cases显示文摘 | Spaggiari L Leo F Giulia Veronesi G | 2007 | Ann Thorac Surg2007，83，1： | 1 |
| 14 | The pilocarpine model of temporal lobe epilepsy 显示文摘 | Giulia C Daniela L Giuseppe B | 2008 | Neurosci Methods2008，172，2： | 1 |
| 15 | Variant Philadel- phia translocations: molecular- cytogenetic haracteriza- tion and prognostic influence on frontline imatinib thera- py, a GIMEMA Working Party on CML analysis 显示文摘 | Giulia M Fausto C Simona L | 2011 | Blood2011，117，29： | 1 |
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