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RANBP9 as potential therapeutic target in non-small cell lung cancer

Journal of Cancer Metastasis and Treatment 2020年第1期6卷 177-187页

作者： Anna Tessari Shimaa H.A.Soliman Arturo Orlacchio Marina Capece Joseph M.Amann Rosa Visone David P.Carbone Dario Palmieri Vincenzo coppola Department of Cancer Biology and Genetics College of MedicineThe Ohio State University and Arthur G.James Comprehensive Cancer CenterColumbusOH 43210USA Department of Medicine Dentistry and BiotechnologyG.d’Annunzio University of ChietiChieti 66100Italy Current address:Department of Biochemistry and Molecular Genetics Northwestern University Feinberg School of MedicineChicagoIL 60611USA Division of Medical Oncology Department of Internal MedicineCollege of MedicineThe Ohio State University and Arthur G.James Comprehensive Cancer CenterColumbusOH 43210USA

Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related deaths in the Western *** progress made with targeted therapies and immune checkpoint inhibitors,the vast majority of patients have to undergo chemotherapy with platinum-based *** increase efficacy and reduce potential side effects,a more comprehensive understanding of the mechanisms of the DNA damage response(DDR)is *** have shown that overexpressby live cell imaging Incuyion of the scaffold protein RAN binding protein 9(RANBP9)is pervasive in *** importantly,patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based ***,RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated(ATM)kinase ***,the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging Incuy53 ***9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related(ATR)kinase but not to ATM *** absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase(PARP)resulting in a“BRCAness-like”*** summary,as a result of increased sensitivity to DNA damaging drugs conferred by its ablation in vitro and in vivo,RANBP9 may be considered as a potential target for the treatment of *** article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage,particularly in the context of *** review concludes with future directions and speculative remarks which will need to be addressed in the coming years.

关键词： RANBP9 RANBP10 Scorpins DNA damage DNA repair DNA damage response CTLH complex cisplatin non-small cell lung cancer PARP BRCAness-like phenotype

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Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

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World Journal of Virology 2015年第1期4卷 1-12页

作者： Nicola coppola Salvatore Martini Mariantonietta Pisaturo Caterina Sagnelli Pietro Filippini Evangelista Sagnelli Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples Division of Infectious Diseases AORN Sant’Anna e San Sebastiano di Caserta Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara" Second University of Naples

Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals(DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa(Peg-IFN) + ribavirin(RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCVgenotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.

关键词： Hepatitis C virus infection Human immunodeficiency virus infection Anti-hepatitis C virus treatment Directly acting antivirals HIV/HCV coinfection Chronic hepatitis C

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TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype

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World Journal of Gastroenterology 2016年第38期22卷 8509-8518页

作者： Caterina Sagnelli Marco Merli Caterina Uberti-Foppa Hamid Hasson Anna Grandone Grazia Cirillo Stefania Salpietro Carmine Minichini Mario Starace Emanuela Messina Patrizia Morelli Emanuele Miraglia Del Giudice Adriano Lazzarin Nicola coppola Evangelista Sagnelli Department of Clinical and Experimental Medicine and Surgery F. Magrassi e A. LanzaraSecond University of Naples 80131 Naples Italy Department of Infectious Diseases Vita-Salute University San Raffaele Scientific Institute 20127 Milan Italy Department of Pediatrics Second University of Naples 80131 Naples Italy Department of Mental Health and Public Medicine Section of Infectious Diseases Second University of Naples 80131 Naples Italy

AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected *** The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was *** In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.

关键词： Human immunodeficiency virus/hepatitis C virus co-infection TM6SF2 Liver histology Liver steatosis Liver biopsy

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Surgical treatment of locally advanced anal cancer after male-to-female sex reassignment surgery

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World Journal of Gastroenterology 2009年第23期15卷 2918-2919页

作者： Marco Caricato Fabio Ausania Giovanni Francesco Marangi Ilaria Cipollone Gerardo Flammia Paolo Persichetti Lucio Trodella Roberto coppola Department of General Surgery Campus Bio Medico University of Rome Rome 00139 Italy Plastic and Reconstructive Surgery Campus Bio Medico University of Rome Rome 00139 Italy Radiation Oncology Campus Bio Medico University of Rome Rome 00139 Italy

We present a case of a transsexual patient who underwent a partial pelvectomy and genital reconstruction for anal cancer after chemoradiation. This is the first case in literature reporting on the occurrence of anal cancer after male-to-female sex reassignment surgery. We describe the surgical approach presenting our technique to avoid postoperative complications and preserve the sexual reassignment.

关键词： Sex reassignment Pelvic surgery Analcancer

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Label-free sensing of ultralow-weight molecules with all-dielectric metasurfaces supporting bound states in the continuum

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Photonics Research 2018年第7期6卷 726-733页

作者： SILVIA ROMANO GIANLUIGI ZITO STEFANIA TORINO GIUSEPPE CALAFIORE ERIKA PENZO GIUSEPPE coppola STEFANO CABRINI IVO RENDINA VITO MOCELLA Institute for Microelectronics and Microsystems Unit of Naples National Council of Research Institute of Protein Biochemistry National Council of Research Lawrence Berkeley National Laboratory Molecular Foundry Division

The realization of an efficient optical sensor based on a photonic crystal metasurface supporting bound states in the continuum is reported. Liquids with different refractive indices, ranging from 1.4000 to 1.4480, are infiltrated in a microfluidic chamber bonded to the sensing dielectric metasurface. A bulk liquid sensitivity of 178 nm/RIU is achieved, while a Q-factor of about 2000 gives a sensor figure of merit up to 445 in air at both visible and infrared excitations. Furthermore, the detection of ultralow-molecular-weight(186 Da) molecules is demonstrated with a record resonance shift of 6 nm per less than a 1 nm thick single molecular layer. The system exploits a normal-to-the-surface optical launching scheme, with excellent interrogation stability and demonstrates alignment-free performances, overcoming the limits of standard photonic crystals and plasmonic resonant configurations.

关键词：高效光学传感器折射率理论研究通讯技术

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A randomized double-blind trial on perioperative administration of probiotics in colorectal cancer patients

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World Journal of Gastroenterology 2010年第2期16卷 167-175页

作者： Luca Gianotti Lorenzo Morelli Francesca Galbiati Simona Rocchetti Sara coppola Aldo Beneduce Cristina Gilardini Daniela Zonenschain Angelo Nespoli Marco Braga Department of Surgery Milano-Bicocca University San Gerardo Hopsital Department of Microbiology Università Cattolica Sacro Cuore Department of Surgery San Raffaele University

AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for *** were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before *** same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after *** the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical ***536 was never found at any time-points *** day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ***1 was not found at day+*** observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC

关键词： Probiotic Dendritic cell Microbiota Colon cancer Lymphocyte Surgery Intestinal immunity

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Circulating tumor cells and the metastatic process: the complexity of malignancy

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 628-641页

作者： Tania Di Raimo Elena De Santis Luigi coppola Mario Rosario D’Andrea Francesco Angelini Medical Oncology and Anatomic Pathology Unit San Filippo Neri HospitalRome 00135Italy Experimental&Clinical Pharmacology Centro Di Riferimento Oncologico-National Cancer CenterAviano(PN)33081Italy Department of Anatomical HistologicalLegal Medical and of the Locomotor Apparatus SciencesSapienza UniversityRome 00135Italy Anatomic Pathology Unit Sandro Pertini HospitalRome 00157Italy

Despite improvements achieved in terms of early detection and therapeutic approach,metastatic breast cancer remains one of the principal worldwide causes of *** recent years,due to the heterogeneous response of each patient to chemotherapy,clinical research highlights the need of a personalized *** tumor cells(CTCs)represents a promising tool for this ***,even if their correlation with sever-ity,outcome and metastatic nature of the tumor has been established,several issues,mainly concerning their characterization and isolation,need to be *** this review,latest knowledge on CTCs and metastatic pro-cess in breast cancer were analyzed,aiming to understand their clinical utility and validity for a prospective ther-apeutic scenario.

关键词： Breast cancer metastasis circulating tumor cells personalized therapy

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Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

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World Journal of Gastroenterology 2015年第21期21卷 6698-6705页

作者： Omero Alessandro Paoluzi Giovanna Del Vecchio Blanco Emanuela Visconti Manuela coppola Carla Fontana Marco Favaro Francesco Pallone Gastroenterology Unit Department of Internal MedicineUniversity Tor Vergata Department of Experimental Medicine and Surgery University Tor Vergata

AIM:To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori(***) ***:A total of 142(99 women,43 men; mean 53.0 ± 12.7 years) non-responders to more than two *** eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole,20 mg b.i.d.,levofloxacin,500 mg b.i.d.,and doxycycline,100 mg b.i.d.,randomly associated with(n = 71) or without(n = 71) Lactobacillus casei *** status was checked in all patients at enrollment and at least 8 wk after the end of *** and tolerability of regimens were also ***:*** eradication was achieved in < 50% of patients [per prototol(PP) = 49%; intention to treat(ITT) = 46%].Eradication rate was higher in patients administered probiotics than in those without(PP = 55% vs 43%; ITT = 54% vs 40%).Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%.Therapy was well tolerated,and side effects were generally mild,with only one patient experiencing severe ***:Third-line levofloxacin-doxycycline triple therapy had a low *** eradication efficacy,though the success and tolerability of this treatment may be enhanced with probiotics.

关键词： Doxycycline Eradication therapy Urea breath test Esomeprazole Levofloxacin Helicobacter pylori

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这是下一种能源吗

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经营者(汽车商业评论) 2021年第11期 88-89页

作者：朱琳 Gabrielle coppola ABR

Our Next Energy宣称已解决磷酸铁锂电池动力不足问题,能量密度达287 Wh/L,电芯占比76%2021年10月18日,在电动汽车生产热潮和为提高这些新车的续航能力和成本而进行的创新竞赛中,电池初创公司Our Next Energy (以下简称ONE)表示,它在新...

Our Next Energy宣称已解决磷酸铁锂电池动力不足问题,能量密度达287 Wh/L,电芯占比76%2021年10月18日,在电动汽车生产热潮和为提高这些新车的续航能力和成本而进行的创新竞赛中,电池初创公司Our Next Energy (以下简称ONE)表示,它在新一轮融资中筹集了 2500万美元,由比尔盖茨(Bill Gates)的突破性能源投资公司(Breakthrough Energy Ventures)领投。

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Modelling Weather and Climate Related Fire Risk in Africa

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American Journal of Climate Change 2013年第4期2卷 209-224页

作者： Flávio Justino F.Stordal A.Clement E.coppola A.Setzer D.Brumatti Departamento de Engenharia Agrícola Universidade Federal de ViçosaVicosaBrazil Department of Geosciences University of OsloOsloNorway Department of Earth and Planetary Sciences Johns Hopkins UniversityBaltimoreUSA The Adbus Salam International Centre for Theoretical Physics TriesteItaly National Institute of Space Research S.J.CamposBrazil

Based on regional climate model simulations conducted with RegCM3 and NCEP Reanalyses, the impact of anomalous climate forcing on environmental vulnerability to wildfire occurrence in Africa is analyzed by applying the Potential Fire Index (PFI). Three different model-based vegetation distributions were analyzed for a present day simulation (1980-2000) and for the end of the twenty-first century (2080-2100). It was demonstrated that under current climate and vegetation conditions the PFI is able to reproduce the principal fire risk areas which are concentrated in the Sahelian region from December to March, and in subtropical Africa from July to October. Predicted future changes in vegetation lead to substantial modifications in magnitude of the PFI, particularly for the southern and subtropical region of Africa. The impact of climate changes other than through vegetation, was found to induce more moderate changes in the fire risk, and increase the area vulnerable to fire occurrence in particular in sub-Saharan. The PFI reproduces areas with high fire activity, indicating that this index is a useful tool for forecasting fire occurrence worldwide, because it is based on regionally dependent vegetation and climate factors.

关键词： Climate Changes Soybeans Maize Amazon

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