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Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase

Cancer Drug Resistance 2019年第3期2卷 787-802页

作者： Filippo Merloni nicoletta Ranallo Laura Scortichini Riccardo Giampieri Rossana Berardi Scuola di Specializzazione in Oncologia Universita Politecnica delle MarcheAncona 60121Italy Clinica Oncologica UniversitàPolitecnica delle MarcheAOU Ospedali RiunitiAncona 60126Italy

Fluoropyrimidines are widely used in the treatment of solid tumors, mainly gastrointestinal, head and neck and breast cancer. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for catabolism of 5-FU and it is encoded by DPYD gene. To date, many known polymorphisms cause DPD deficiency and subsequent increase of 5-FU toxicity. In addition, reduced inactivation of 5-FU could lead to increased 5-FU intracellular concentration and augmented efficacy of this drugs. Therefore DPD expression, particularly intratumoral, has been investigated as predictive and prognostic marker in 5-FU treated patients. There also seems to be a tendency to support the correlation between DPD expression and response/survival in patients treated with fluoropyrimidine even if definitive conclusions cannot be drawn considering that some studies are conflicting. Therefore, the debate on intratumoral DPD expression as a potential predictor and prognostic marker in patients treated with fluoropyrimidines is still open. Four DPD-polymorphisms are the most relevant for their frequency in population and clinical relevance. Many studies demonstrate that treating a carrier of one of these polymorphisms with a full dose of fluoropyrimidine can expose patient to a severe, even life-threatening, toxicity. Severe toxicity is reduced if this kind of patients received a dose-adjustment after being genotyped. CPIC (Clinical Pharmacogenetics Implementation Consortium) is an International Consortium creating guidelines for facilitating use of pharmacogenetic tests for patient care and helps clinicians ensuring a safer drug delivery to the patient. Using predictive DPD deficiency tests in patients receiving 5FU-based chemotherapy, in particular for colorectal cancer, has proven to be a cost-effective strategy.

关键词： 5-fluorouracil fluoropyrimidines chemotherapy dihydropyrimidine dehydrogenase dihydropyrimidine dehydrogenase DPYD CPIC polymorphisms

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Mirror,mirror on the wall,who is the best of them all?Artificial intelligence versus gastroenterologists in solving clinical problems

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Gastroenterology Report 2023年第1期11卷 579-581页

作者： Felice Benedicenti Tommaso Pessarelli Mattia Corradi Marco Michelon nicoletta Nandi Pietro Lampertico Maurizio Vecchi Lucia Scaramella Luca Elli Department of Pathophysiology and Transplantation University of MilanMilanItaly Gastroenterology and Endoscopy Unit Foundation IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly Division of Gastroenterology and Hepatology CRC“A.M.and A.Migliavacca”Center for the Study of Liver DiseaseFoundation IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly

Introduction Artificial intelligence(AI)is a concept that commonly refers to machines mimicking human cognitive behavior during learning and problem-solving[1].Chatbots are a typical example of an AI system,capable of interacting with humans[2].ChatGPT(OpenAI,San Francisco,CA,USA)[3]is a new-generation chatbot that captures the context and relationship between words in input sequences through multiple layers of self-attention and feedforward neural ***,it predicts the most likely“token”to succeed the previous one based on patterns in its training ***,it is a self-contained system that does not copy existing information[4].

关键词： token neural mirror

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A Comparative Study of Human and Animal Hairs:Microscopic Hair Comparison and Cytochrome c Oxidase I Species Identification

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Journal of Forensic Science and Medicine 2019年第1期5卷 20-23页

作者： Venusia Cortellini Anna Carobbio Gloria Brescia nicoletta Cerri Andrea Verzeletti Department of Medical and Surgical Specialties Radiological Sciences and Public HealthForensic Medicine UnitUniversity of BresciaBresciaItaly

Human and animal hairs have been used in forensic investigations for over a *** is stable under adverse natural conditions;hence,it is often recovered at the crime scene,and it is necessary to determine whether the hair is of human or animal *** and genetic characteristics are useful to differentiate human hair from animal *** the present study,we analyzed the distinguishing characteristics of hair of various *** addition,we explore species identification by cytochrome c oxidase I mitochondrial gene *** confirm that both the microscopic and molecular analyses of hairs are useful in forensic investigations.

关键词： Cytochrome c oxidase I hair optical microscope species identification

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Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

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World Journal of Hepatology 2018年第9期10卷 558-570页

作者： Evangelista Sagnelli nicoletta Potenza Lorenzo Onorato Caterina Sagnelli Nicola Coppola Aniello Russo Department of Mental Health and Public Medicine Section of Infectious DiseasesUniversity of Campania Luigi Vanvitelli DISTABIF University of Campania "Luigi Vanvitelli"

MicroRNAs(miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level by affecting both the stability and translation of complementary mRNAs. Several studies have shown that mi RNAs are important regulators in the conflicting efforts between the virus(to manipulate the host for its successful propagation) and the host(to inhibit the virus),culminating in either the elimination of the virus or its persistence. An increasing number of studies report a role of miRNAs in hepatitis B virus(HBV) replication and pathogenesis. In fact,HBV is able to modulate different host miRNAs,particularly through the transcriptional transactivator HBx protein and,conversely,different cellular miRNAs can regulate HBV gene expression and replication by a direct binding to HBV transcripts or indirectly targeting host factors. The present review will discuss the role of miRNAs in the pathogenesis of HBVrelated diseases and their role as a biomarker in the management of patients with HBV-related disease and as therapeutic targets.

关键词： Hepatitis B virus infection MicroRNAs Hepatitis B virus pathogenesis Molecular mechanisms

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Bcl-2 down modulation in WEHI-3B/CTRES cells resistant to Cholera Toxin(CT)-induced apoptosis

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Cell Research 2006年第3期16卷 306-312页

作者： Augusto Pessina Cristina Croera nicoletta Savalli Arianna Bonomi Loredana Cavicchini Elisa Turlizzi Fabiana Guizzardi Lucia Guido Laura Daprai Maria GraziaNeri Institute of Microbiology University of MilanVia Pascal 3620133 MilanItaly ECVAM Institute for Health and Consumer ProtectionEuropean Commission Joint Research CentreIspra 21020Italy UCLA Department of AnesthesiologyLos AngelesCA 90095USA

The very different effects of Cholera Toxin (CT) on cell growth and proliferation may depend on the type of ganglio-side receptors in cell membranes and different signal transduction mechanisms triggered,but other functions relatedto the drug resistance mechanisms can not be *** effect of CT treatment on the "in vitro" clonogenicity,thePopulation Doubling Time (PDT),apoptosis,PKA activation and Bax and Bcl-2 expression was evaluated in WEHI-3Bcell line and its CT-resistant subclone (WEHI-3B/CTRES).In WEHI-3B parental cells the dramatic accumulation ofcAMP induced by CT correlated well with PKA activation,increased PDT value,inhibition of clonogenicity and apop-tosis.H-89 treatment inhibited PKA activation by CT but did not protect the cells from apoptosis and growth *** WEHI-3B/CTRES no significant CT-dependent accumulation of cAMP occurred with any increase of PKA activityand *** CT resistant cells (WEHI-3B/CTRES),Bcl-2 expression was down regulated by both CT or drug treatment(eg.,ciprofloxacin,CPX) although these cells were protected from CT-dependent apoptosis but not from *** from other cell models described,down regulation of Bcl-2 is proved to be independent on cAMPaccumulation and PKA *** observations support the implication of cAMP dependent kinase (PKA) in theinhibition of WEHI-3B cells growth and suggest that,in WEHI-3B/CTRES,Bcl-2 expression could be modulated byCT in the absence of cAMP *** in consideration of many contradictory data reported in literature,ourcell models(of one sensitive parental cell strain and two clones with different uncrossed specific resistance to CT andCPX)provides a new and interesting tool for better investigating the relationship between the CT signal transductionmechanisms and Bcl-2 expression and function.

关键词： cholera toxin Bcl-2 PKA apoptosis ciprofloxacin resistance

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Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2cm

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World Journal of Gastroenterology 2011年第26期17卷 3126-3132页

作者： Maurizio Pompili Erica Nicolardi Valeria Abbate Luca Miele Laura Riccardi Marcello Covino nicoletta De Matthaeis Antonio Grieco Raffaele Landolfi Gian Ludovico Rapaccini Department of Internal Medicine Università Cattolica del Sacro Cuore Department of Emergency Università Cattolica del Sacro Cuore

AIM:To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol ***:One-hundred forty-eight patients with solitary hepatocellular carcinoma were *** tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 *** impact of some pretreatment clinical and laboratory parameters and of tumor recurrence on patients' survival was ***:Among the pre-treatment parameters,only a tumor diameter of less than 2 cm was an independent prognostic factor of *** occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate *** with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulativesurvival(73.0% vs 47.9%)(P = 0.009),3-year local recurrence rate(29.1% vs 51.5%)(P = 0.011),and 5-year distant intrahepatic recurrence rate(52.9% vs 62.8%)(P = 0.054) compared to patients with a larger ***:The 5-year survival rate of patients with single hepatocellular carcinoma < 2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

关键词：注射治疗无水乙醇肝癌单因素分析射频消融生存率复发率患者

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High-fibre diet and Lactobacillus paracasei B21060 in symptomatic uncomplicated diverticular disease

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World Journal of Gastroenterology 2012年第41期18卷 5918-5924页

作者： Edith Lahner Gianluca Esposito Angelo Zullo Cesare Hassan Claudio Cannaviello Maria Carla Di Paolo Lorella Pallotta nicoletta Garbagna Enzo Grossi Bruno Annibale Department of Digestive and Liver Disease University SapienzaRome 2nd Medical SchoolSant'Andrea Hospital00189 RomeItaly Ospedale Nuovo Regina Margherita 00189 RomeItaly Gastroenterology Unit Ospedale Israelitico00148 RomeItaly Gastroenterology Unit Ospedale San Giovanni00184 RomeItaly Medical Department Bracco Spa 20134 MilanItaly

AIM:To investigate in symptomatic uncomplicated diverticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal ***:This study was a multicentre,6-mo randomized,controlled,parallel-group intervention with a preceding 4-wk washout *** outpatients with symptomatic uncomplicated diverticular disease,aged 40-80 years,evaluated in 4 Gastroenter-ology Units,were *** uncomplicated diverticular disease patients were randomized to two treatment arms A or *** A(n = 24 patients) received 1 symbiotic sachet Flortec(Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 *** B(n = 21 patients) received high-fibre diet alone for 6 *** primary endpoint was regression of abdominal symptoms and change of symptom severity after 3 and 6 mo of ***:In group A,the proportion of patients with abdominal pain 24 h decreased from 60% to 20% then 5% after 3 and 6 mo,respectively in group A(P < 0.001) and from 33.3% to 9.5% at both 3 and 6 mo in group B(P = 0.03).In group A the proportion of patients with abdominal bloating significantly decreased from 95% to 60% after 3 mo,and remained stable(65%) at 6-mo follow-up(P = 0.005) while in group B,no significant changes in abdominal bloating was observed(P = 0.11).After 6 mo of treatment,the mean visual analogic scale(VAS) values of both short-lasting abdominal pain(VAS,mean ± SD,group A:4.6 ± 2.1 vs 2.2 ± 0.8,P = 0.02;group B:4.6 ± 2.9 vs 2.0 ± 1.9,P = 0.03) and abdominal bloating(VAS,mean ± SD,group A:5.3 ± 2.2 vs 3.0 ± 1.7,P = 0.005;group B:

关键词：饮食治疗疾病症状干酪乳杆菌高纤维并发症 VAS 胃肠病学随机分配

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The "Net" in Education:some operative examples

The "Net" in Education:some operative examples

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2001 International Conferences on Info-tech and Info-net

作者： nicoletta Sala University of Italian Switzerland Academy of Architecture CH 6850 Mendrisio-Switzerland

＜正＞The Internet has become an invaluable resource in teaching and learning activities both within academic and non academic *** can be used to conduct research,seek out information for course preparation, deliver courses and facilitate communication between students and teaching *** aim of this paper is to present two different experiences which involve the Internet in educational paths in high school and *** first experience,named Web Learning Environment（WLE）,we have studied the use of the Internet and its resources to develop a new learning *** have involved a classroom（sixteen students,aged 16-17） of a technical institute in Italy（specialisation in Information Technologies）.The project has been divided in six different phases:the knowledge of the Internet,the research in the Internet,the access to the FTP,the didactics with the Internet,the communication using the "Net",and the creation of a cooperative hypertext dedicated to the Bonaventura Cavalieri（an Italian mathematician）.Second experience, named "Cybermath",is an attempt to build some hypermedia modules to introduce the *** has been developed at the Academy of Architecture of Mendrisio（University of Italian Switzerland）,Switzerland.

关键词： Internet Learning Environment Cooperative Learning Cybermath

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Coupling effects in QD dimers at sub-nanometer interparticle distance

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Nano Research 2020年第4期13卷 1071-1080页

作者： Carlo Nazareno Dibenedetto Elisabetta Fanizza Rosaria Brescia Yuval Kolodny Sergei Remennik Annamaria Panniello nicoletta Depalo Shira Yochelis Roberto Comparelli Angela Agostiano Maria Lucia Curri Yossi Paltiel Marinella Striccoli CNR-Istituto per i Processi Chimico-Fisici SS Bari Via Orabona 470125-BariItaly Dipartimento di Chimica Universita degli Studi di Bari Aldo MoroVia Orabona 470125-BariItaly Electron Microscopy Facility Istituto Italiano di Tecnologiavia Morego 3016163 GenovaItaly Department of Applied Physics and the Center for Nanoscience and Nanotechnology Hebrew University of JerusalemJerusalem 9190401Israel

Currently,intensive research efforts focus on the fabrication of meso-structures of assembled colloidal quantum dots(QDs)with original optical and electronic *** collective features originate from the QDs coupling,depending on the number of connected units and their ***,the development of general methodologies to assemble colloidal QD with precise stoichiometry and particle-particle spacing remains a key ***,we demonstrate that dimers of CdSe QDs,stable in solution,can be obtained by engineering QD surface chemistry,reducing the surface steric hindrance and favoring the link between two *** connection is made by using alkyl dithiols as bifunctional linkers and different chain lengths are used to tune the interparticle distance from few nm down to 0.5 *** spectroscopic investigation highlights that coupling phenomena between the QDs in dimers are strongly dependent on the interparticle distance and QD size,ultimately affecting the exciton dissociation efficiency.

关键词： quantum dots dimers surface chemistry dithiols coupling

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铜/二氧化硅催化剂中金属纳米粒子构性关系的一些认识（英文）

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Chinese Journal of Catalysis 2019年第11期40卷 1788-1794页

作者： Nicola Scotti Elisabetta Finocchio Claudio Evangelisti Marcello Marelli Rinaldo Psaro nicoletta Ravasio Federica Zaccheria 国家研究委员会演技中心分子科学与技术研究所催化实验室意大利米兰20133 热那亚大学理工学院土木工程与环境化学系(DICCA)意大利热那亚16145

考察了化学吸附水解法制备的两种铜/二氧化硅催化剂上3-甲基环己酮加氢反应活性.发现两种催化剂在60℃和1bar H2下催化活性非常高.吸附CO红外光谱和透电镜结果表明,催化剂中存在结晶良好的铜颗粒.通过假设一个立方八面体模型,我们可以... 详细信息

考察了化学吸附水解法制备的两种铜/二氧化硅催化剂上3-甲基环己酮加氢反应活性.发现两种催化剂在60℃和1bar H2下催化活性非常高.吸附CO红外光谱和透电镜结果表明,催化剂中存在结晶良好的铜颗粒.通过假设一个立方八面体模型,我们可以证明加氢活性与金属颗粒上的高配位点有关.本文还与蒸氨法制备的样品进行了比较,发现在相同的实验条件下,蒸氨法样品在加氢反应中没有活性.

关键词：铜颗粒金属粒子形态 Lewis酸位加氢双功能催化剂

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