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| 1 | Treatment of gastric cancer显示文摘The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the second leading cause of cancer death worldwide.Surgery remains the only curative therapy,while perioperative and adjuvant chemotherapy,as well as chemoradiation,can improve outcome of resectable gastric cancer with extended lymph node dissection.More than half of radically resected gastric cancer patients relapse locally or with distant metastases,or receive the diagnosis of gastric cancer when tumor is disseminated;therefore,median survival rarely exceeds12 mo,and 5-years survival is less than 10%.Cisplatin and fluoropyrimidine-based chemotherapy,with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients,is the widely used treatment in stageⅣpatients fit for chemotherapy.Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance | Michele Orditura Gennaro Galizia Vincenzo Sforza Valentina Gambardella Alessio Fabozzi Maria Maddalena Laterza Francesca Andreozzi Jole Ventriglia Beatrice Savastano Andrea Mabilia Eva Lieto Fortunato Ciardiello Ferdinando De Vita | 2014 | World Journal of Gastroenterology2014，20，7： | 116 |
| 2 | Clinical management of advanced gastric cancer: The role of new molecular drugs显示文摘Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States.Surgery represents the main approach for this disease but,notwithstanding the advances in surgical techniques,we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates.Despite the development of new drugs has significantly improved the effectiveness of chemothera-py,the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor.Recently,several molecular target agents have been investigated;in particular,trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients.New molecules targeting vascular epithelial growth factor,mammalian target of rapamycin,and anti hepatocyte growth factor-c-Met pathway are also under investigation,with interesting results.Anyway,it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results.In this paper we review the actual'scenario'of targeted treatments,also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma,discussing their efficacy and potential applications in clinical practice. | Ferdinando De Vita Natale Di Martino Alessio Fabozzi Maria Maddalena Laterza Jole Ventriglia Beatrice Savastano Angelica Petrillo Valentina Gambardella Vincenzo Sforza Luigi Marano Annamaria Auricchio Gennaro Galizia Fortunato Ciardiello Michele Orditura | 2014 | World Journal of Gastroenterology2014，20，40： | 12 |
| 3 | Implication of the Hedgehog pathway in hepatocellular carcinoma显示文摘The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis,proliferation and progression of HCC.Among all of the pathways that are involved in the development of HCC,Hedgehog(HH)signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression.HH plays a physiological role in embryogenesis,through the induction of the differentiation of hepatocytes from endodermal progenitors.The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development.HH activation sustains the subpopulation of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC,and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells.High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome.In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth,metastasis and a mesenchymal phenotype. | Carminia Maria Della Corte Giuseppe Viscardi Federica Papaccio Giovanna Esposito Giulia Martini Davide Ciardiello Erika Martinelli Fortunato Ciardiello Floriana Morgillo | 2017 | World Journal of Gastroenterology2017，23，24： | 10 |
| 4 | Treatment of esophagogastric junction carcinoma:An unsolved debate显示文摘The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening programs to individuate and eradicate BE represent the best way to reduce AEG cancer. Several endoscopic approaches are here discussed. Surgicalstrategies for different types of AEG cancer are now fairly standardized, and multidisciplinary strategies u s i n g c h e m o t h e ra py o r c h e m o ra d i o t h e ra py m ay improve the outcome of these patients. Here we briefly discuss the keypoints, main topics, and critical issues, according to accumulating evidence and taking into account our own experience. | Michele Orditura Gennaro Galizia Eva Lieto Ferdinando De Vita Fortunato Ciardiello | 2015 | World Journal of Gastroenterology2015，21，15： | 10 |
| 5 | Present and future of metastatic colorectal cancer treatment: A review of new candidate targets显示文摘In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer(m CRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients present with metastasis at the time of diagnosis or relapse after a few months. The complex molecular heterogeneity of this disease is not completely understood; to date, there is a lack of predictive biomarkers that can be used to select subsets of patients who may respond to target drugs. Only the RAS-mutation status is used to predict resistance to anti-epidermal growth factor receptor agents in patients with m CRC. In this review, we describe approved targeted therapies for the management of metastatic m CRC and discuss new candidate targets on the horizon. | Giulia Martini Teresa Troiani Claudia Cardone Pietropaolo Vitiello Vincenzo Sforza Davide Ciardiello Stefania Napolitano Carminia Maria Della Corte Floriana Morgillo Antonio Raucci Antonio Cuomo Francesco Selvaggi Fortunato Ciardiello Erika Martinelli | 2017 | World Journal of Gastroenterology2017，23，26： | 7 |
| 6 | 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 |
| 7 | Towards maximized utilization of iridium for the acidic oxygen evolution reaction显示文摘The reduction in noble metal content for efficient oxygen evolution catalysis is a crucial aspect towards the large scale commercialisation of polymer electrolyte membrane electrolyzers.Since catalytic stability and activity are inversely related,long service lifetime still demands large amounts of low-abundant and expensive iridium.In this manuscript we elaborate on the concept of maximizing the utilisation of iridium for the oxygen evolution reaction.By combining different tin oxide based support materials with liquid atomic layer deposition of iridium oxide,new possibilities are opened up to grow thin layers of iridium oxide with tuneable noble metal amounts.In-situ,time-and potential-resolved dissolution experiments reveal how the stability of the substrate and the catalyst layer thickness directly affect the activity and stability of deposited iridium oxide.Based on our results,we elaborate on strategies how to obtain stable and active catalysts with maximized iridium utilisation for the oxygen evolution reaction and demonstrate how the activity and durability can be tailored correspondingly.Our results highlight the potential of utilizing thin noble metal films with earth abundant support.materials for future catalytic applications in the energy sector. | Marc Ledendecker Simon Geiger Katharina Hengge Joohyun Lim Serhiy Cherevko Andrea M. Mingers Daniel Gohl Guilherme V. Fortunato Daniel Jalalpoor Ferdi Schuth Christina Scheu Karl J. J. Mayrhofer | 2019 | Nano Research2019，12，9： | 6 |
| 8 | A one-dimensional polynomial chaos method in CFD–Based uncertainty quantification for ship hydrodynamic performance显示文摘A one-dimensional non-intrusive Polynomial Chaos(PC)method is applied in Uncertainty Quantification(UQ)studies for CFD–based ship performances simulations.The uncertainty properties of Expected Value(EV)and Standard Deviation(SD)are evaluated by solving the PC coefficients from a linear system of algebraic equations.The one-dimensional PC with the Legendre polynomials is applied to:(1)stochastic input domain and(2)Cumulative Distribution Function(CDF)image domain,allowing for more flexibility.The PC method is validated with the Monte-Carlo benchmark results in several high-fidelity,CFD-based,ship UQ problems,evaluating the geometrical,operational and environmental uncertainties for the Delft Catamaran 372.Convergence is studied versus PC order P for both EV and SD,showing that high order PC is not necessary for present applications.Comparison is carried out for PC with/without the least square minimization when solving the PC coefficients.The least square minimization,using larger number of CFD samples,is recommended for current test cases.The study shows the potentials of PC method in Robust Design Optimization(RDO)and Reliability-Based Design Optimization(RBDO)of ship hydrodynamic performances. | 贺伟 DIEZ Matteo CAMPANA Emilio Fortunato STERN Frederick 邹早建 | 2013 | Journal of Hydrodynamics2013，25，5： | 5 |
| 9 | Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials显示文摘 | Carsten Bokemeyer Eric Van Cutsem Philippe Rougier Fortunato Ciardiello Steffen Heeger Michael Schlichting Ilhan Celik Claus-Henning K?hne | 2012 | European Journal of Cancer2012，，10： | 5 |
| 10 | KRAS , BRAF , PIK3CA , and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer显示文摘 | Wendy De Roock Veerle De Vriendt Nicola Normanno Fortunato Ciardiello Sabine Tejpar | 2011 | Lancet Oncology2011，，6： | 3 |
| 11 | Clinical and molecular spectrum of Wiedemann-Steiner syndrome, an emerging member of the chromatinopathy family显示文摘Wiedemann-Steiner syndrome(OMIM#605130)is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature;consistent facial features,including long eyelashes,thick or arched eyebrows with a lateral flare,wide nasal bridge,and downslanting and vertically narrow palpebral fissures;mild to moderate intellectual disability;behavioral difficulties;and hypertrichosis on the back.It is caused by heterozygous pathogenic variants in KMT2A.This gene has an established role in histone methylation,which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies,a heterogeneous group of syndromic conditions that share a common trigger:The disruption of one of the genes involved in chromatin modification,leading to dysfunction of the epigenetic machinery. | Paolo Fontana Francesco Fioravanti Passaretti Marianna Maioli Giuseppina Cantalupo Francesca Scarano Fortunato Lonardo | 2020 | World Journal of Medical Genetics2020，9，1： | 2 |
| 12 | Optimizing treatment of metastatic colorectal cancer patients with anti-EGFR antibodies: overcoming the mechanisms of cancer cell resistance显示文摘 | Teresa Troiani Silvia Zappavigna Erika Martinelli Santolo R. Addeo Paola Stiuso Fortunato Ciardiello Michele Caraglia | 2013 | Expert Opinion on Biological Therapy2013，，2： | 2 |
| 13 | Safety and efficacy of sorafenib in patients with advanced hepatocellularcarcinoma and Child-Pugh A or B cirrhosis显示文摘 | Alessandro Federico Michele Orditura Gaetano Cotticelli Ilario De Sio Marco Romano Antonietta Gravina Marcello Dallio Alessio Fabozzi Fortunato Ciardiello Carmela Loguercio Ferdinando De Vita | 2015 | Oncology Letters2015，，4： | 2 |
| 14 | Evaluation of antibody-dependent cell-mediatedcy totoxicity activity and cetuximab response in KRAS wildtype metastatic colorectal cancer patients显示文摘AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients. | cristiana lo nigro vincenzo ricci daniela vivenza martino monteverde giuliana strola francesco lucio federica tonissi emanuela miraglio cristina granetto mirella fortunato marco carlo merlano | 2016 | World Journal of Gastrointestinal Oncology2016，8，2： | 2 |
| 15 | Increased flow and shear stress enhance in vivo transforming growth factor-betal after experimental arterial injury 显示文摘 | Song RH Kocharyan HK Fortunato JE | 2000 | Arterioscler Thromb Vasc Bilo2000，20，4： | 2 |
| 16 | A mutation in the ZNF687 gene that is responsible for the severe form of Paget's disease of bone causes severely altered bone remodeling and promotes hepatocellular carcinoma onset in a knock-in mouse model显示文摘Paget’s disease(PDB)is a late-onset bone remodeling disorder with a broad spectrum of symptoms and complications.One of the most aggressive forms is caused by the P937R mutation in the ZNF687 gene.Although the genetic involvement of ZNF687 in PDB has been extensively studied,the molecular mechanisms underlying this association remain unclear.Here,we describe the first Zfp687 knock-in mouse model and demonstrate that the mutation recapitulates the PDB phenotype,resulting in severely altered bone remodeling.Through microcomputed tomography analysis,we observed that 8-month-old mutant mice showed a mainly osteolytic phase,with a significant decrease in the trabecular bone volume affecting the femurs and the vertebrae.Conversely,osteoblast activity was deregulated,producing disorganized bone.Notably,this phenotype became pervasive in 16-month-old mice,where osteoblast function overtook bone resorption,as highlighted by the presence of woven bone in histological analyses,consistent with the PDB phenotype.Furthermore,we detected osteophytes and intervertebral disc degeneration,outlining for the first time the link between osteoarthritis and PDB in a PDB mouse model.RNA sequencing of wild-type and Zfp687 knockout RAW264.7 cells identified a set of genes involved in osteoclastogenesis potentially regulated by Zfp687,e.g.,Tspan7,Cpe,Vegfc,and Ggt1,confirming its role in this process.Strikingly,in this mouse model,the mutation was also associated with a high penetrance of hepatocellular carcinomas.Thus,this study established an essential role of Zfp687 in the regulation of bone remodeling,offering the potential to therapeutically treat PDB,and underlines the oncogenic potential of ZNF687. | Sharon Russo Federica Scotto di Carlo Antonio Maurizi Giorgio Fortunato Anna Teti Danilo Licastro Carmine Settembre Tommaso Mello Fernando Gianfrancesco | 2023 | Bone Research2023，11，1： | 2 |
| 17 | Epidermal growth factor-related peptides and their receptors in human malignancies显示文摘 | David S. Salomon Ralf Brandt Fortunato Ciardiello Nicola Normanno | 1995 | Critical Reviews in Oncology and Hematology1995，，3： | 2 |
| 18 | Oxide Semiconductor Thin‐Film Transistors: A Review of Recent Advances显示文摘 | E. Fortunato P. Barquinha R. Martins | 2012 | Mater2012，，22： | 2 |
| 19 | Community detection in graphs显示文摘 | Santo Fortunato | 2009 | Physics Reports2009，，3： | 2 |
| 20 | Tissue engineering for neuromuscular disorders of the gastrointestinal tract显示文摘The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach;the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation. | Kenneth L Koch Khalil N Bitar John E Fortunato Khalil N Bitar | 2012 | World Journal of Gastroenterology2012，18，47： | 2 |
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