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Multiple cells of origin in cholangiocarcinoma underlie biological,epidemiological and clinical heterogeneity

World Journal of Gastrointestinal Oncology 2012年第5期4卷 94-102页

作者： Vincenzo Cardinale guido carpino Lola Reid Eugenio Gaudio Domenico Alvaro Department of MedicoSurgical Sciences and Biotechnologies Polo PontinoSapienza University of Rome00137 RomeItaly Department of Health Sciences University of Rome "Foro Italico"000135 RomeItaly Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of Rome000137 RomeItaly Department of Cell and Molecular Physiology Biomedical EngineeringProgram in Molecular Biology and BiotechnologyUNC School of MedicineChapel HillNC 27599United States Eleonora Lorillard Spencer-Cenci Foundation 00156 RomeItaly

Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological features.Furthermore,different stem cell niches have been recently described in the liver and biliarytree,suggesting this as the basis of the heterogeneity of intrahepatic(IH)-and extrahepatic(EH)-CCAs,which are two largely different tumors from both biological and epidemiological points of view.The complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver tumors.These recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic,prognostic and,hopefully,therapeutic categories of IH-and EH-CCAs.

关键词： Intrahepatic cholangiocarcinoma Extrahepatic cholangiocarcinoma Cholangiocarcinoma classification Cholangiolocarcinoma Cells of origin Cancer stem cells Peribiliary glands Biliary tree stem/progenitor cells Human hepatic stem cells Risk factors Targeted therapies

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Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

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World Journal of Gastroenterology 2019年第31期25卷 4343-4359页

作者： Piera Zaccari Vincenzo Cardinale Carola Severi Federica Pedica guido carpino Eugenio Gaudio Claudio Doglioni Maria Chiara Petrone Domenico Alvaro Paolo Giorgio Arcidiacono Gabriele Capurso Department of Internal Medicine and Medical Specialties Gastroenterology UnitSapienza University of RomeRome 00161Italy Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome00161 RomeItaly Pathology Department Pancreas Translational and Clinical Research CenterSan Raffaele Scientific Institute IRCCSMilan 20132Italy Department of Movement Human and Health SciencesDivision of Health SciencesUniversity of Rome"Foro Italico"Rome 00161Italy Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesDivision of Human AnatomySapienza University of RomeRome 00161Italy PancreatoBiliary Endoscopy and EUS Division Pancreas Translational and Clinical Research CenterSan Raffaele Scientific Institute IRCCSMilan 20132Italy Department of Translational and Precision Medicine Sapienza University of RomeRome 00161Italy

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular,histological and pathophysiological features.Intraepithelial neoplasms are reported in biliary tract,as biliary intraepithelial neoplasm(BilIN),and in pancreas,as pancreatic intraepithelial neoplasm(PanIN).Both can evolve to invasive carcinomas,respectively cholangiocarcinoma(CCA)and pancreatic ductal adenocarcinoma(PDAC).Intraductal papillary neoplasms arise in biliary tract and pancreas.Intraductal papillary neoplasm of the biliary tract(IPNB)share common histologic and phenotypic features such as pancreatobiliary,gastric,intestinal and oncocytic types,and biological behavior with the pancreatic counterpart,the intraductal papillary mucinous neoplasm of the pancreas(IPMN).All these neoplastic lesions exhibit similar immunohistochemical phenotypes,suggesting a common carcinogenic process.Indeed,CCA and PDAC display similar clinic-pathological features as growth pattern,poor response to conventional chemotherapy and radiotherapy and,as a consequence,an unfavorable prognosis.The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.

关键词： Biliary Pancreatic Progenitors Preneoplastic Common Tumor

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Cholangiocytes and blood supply

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World Journal of Gastroenterology 2006年第22期12卷 3546-3552页

作者： Eugenio Gaudio Antonio Franchitto Luigi Pannarale guido carpino Gianfranco Alpini Heather Francis Shannon Glaser Domenico Alvaro Paolo Onori Department of Human Anatomy University of Rome "La Sapienza" RomeItaly Central Texas Veterans Health Care System and Department of Medicine and Systems Biology and Translational Medicine College of MedicineTempleTXUnited States Division of Research and Education Scott & White Hospital and The Texas A&M University System Health Science Center College of MedicineTempleTXUnited States Department of Medicine and Division of Research and Education Scott & White Hospital and The Texas A&M University System Health Science Center College of MedicineTempleTXUnited States Division of Gastroenterology University of Rome "La Sapienza" RomeItaly University of Rome "La Sapienza" Polo PontinoLatinaItaly Department of Experimental Medicine Section of Human and Clinical Anatomy State University of L'AquilaL'AquilaItaly

胆汁的树的微脉管的供应，仙子胆管丛(PBP ) ，源自肝的动脉树枝和流动进肝窦状隙。PBP 的详细三维的研究被使用扫描电子执行了显微镜学脉管的腐蚀演员组(SEMvcc ) 技术。认为 PBP 在支持胆汁的上皮的能分泌、吸收性的功能起一个基本作... 详细信息

胆汁的树的微脉管的供应，仙子胆管丛(PBP ) ，源自肝的动脉树枝和流动进肝窦状隙。PBP 的详细三维的研究被使用扫描电子执行了显微镜学脉管的腐蚀演员组(SEMvcc ) 技术。认为 PBP 在支持胆汁的上皮的能分泌、吸收性的功能起一个基本作用，他们在常态和病理的组织被探索。正常的肝证明 PBP 安排在 extra-附近 -- 并且肝内的胆汁的树。在小门道， PBP 被日益增多地继续了它显示出一个更复杂的脉管的网络的额外的肝的 PBP 的 capillaries 的单个层描绘。在普通的管结扎(BDL ) 以后，胆汁管和 PBP 增长的进步修正被观察。PBP 介绍在许多胆汁管附近安排的一个三维的网络并且作为容器的捆出现，由有典型圆网孔结构的同类的直径的 capillaries 镇静。PBP 网络从显得正常的正弦曲线网络是容易可区分的。在 BDL 期间考虑 PBP 的庞大的延期，脉管的内皮生长因素(VEGF ) 起的可能的作用被评估。VEGF -- A， VEGF-C 和他们的相关受体高度出现了在 BDL 老鼠的增殖的 cholangiocytes 积极的免疫。到象肝的动脉结扎一样的 BDL 老鼠的 anti-VEGF-A 或 anti-VEGF-C 抗体的管理导致了一个减少的胆汁管团。rVEGF 的管理 -- 到 BDL 肝的动脉的 A 绑扎老鼠阻止了 cholangiocyte 增长和 VEGF 的减少 -- 表情作为与 BDL 控制老鼠相比。这些数据处于 cholangiocyte 增长的条件建议胆汁的树的动脉的血供给的角色，例如它发生在长期的胆汁郁积期间。在另一方面， VEGF 作为在 cholangiocytes 和 PBP endothelial 之间的串音的一个工具起的作用建议 VEGF 版本和功能的那操作能为肝的动脉或胆汁的树的损坏描绘的人的病理学的条件代表治疗学的策略。

关键词：血液供给肝疾病静脉血管病理机制

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Role of sex hormones in the modulation of cholangiocyte function

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World Journal of Gastrointestinal Pathophysiology 2010年第2期1卷 50-62页

作者： Romina Mancinelli Paolo Onori Sharon DeMorrow Heather Francis Shannon Glaser Antonio Franchitto guido carpino Gianfranco Alpini Eugenio Gaudio Department of Human Anatomy University of Rome "La Sapienza" Department of Experimental Medicine University of L'Aquila Scott and White Digestive Disease Research Center Texas A&M Health Science CenterCollege of Medicine Department of Health Science University of Rome "Foro Italico"Rome 00135Italy Research Central Texas Veterans Health Care System

Over the last years,cholangiocytes,the cells that line the biliary tree,have been considered an important object of study for their biological properties which involves bile formation,proliferation,injury repair,fibrosis and angiogenesis.Cholangiocyte proliferation occurs in all pathologic conditions of liver injury where it is associated with inflammation and regeneration.During these processes,biliary cells start to secrete different cytokines,growth factors,neuropeptides and hormones which represent potential mechanisms for cross talk with other liver cells.Several studies suggest that hormones,and in particular,sex hormones,play a fundamental role in the modulation of the growth of this compartment in the injured liver which functionally conditions the progression of liver disease.Understanding the mechanisms of action and the intracellular pathways of these compounds on cholangiocyte pathophysiology will provide new potential strategies for the management of chronic liver diseases.The purpose of this review is to summarize the recent findings on the role of sex hormones in cholangiocyte proliferation and biology.

关键词： Biliary epithelium Sex hormones Cholestatic diseases

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Intrahepatic cholangiocarcinoma: review and update

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Hepatoma Research 2018年第6期4卷 25-40页

作者： Vincenzo Cardinale Maria Consiglia Bragazzi guido carpino Sabina Di Matteo Diletta Overi Lorenzo Nevi Eugenio Gaudio Domenico Alvaro Department of Medico-Surgical Sciences and Biotechnologies Polo PontinoSapienza University of RomeRome 00198Italy Department of Movement Human and Health SciencesDivision of Health SciencesUniversity of Rome“Foro Italico”Rome 00100Italy Department of Medicine and Medical Specialties Sapienza University of RomeRome 00198Italy Division of Human Anatomy Department of AnatomicalHistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRome 00198Italy

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its anatomical location. Of note, these three CCA subtypes have common features but also important inter-tumor and intra-tumor differences that can affect the pathogenesis and outcome. A unique feature of iCCA is that it recognizes as origin tissues, the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, which are furnished by two distinct stem cell niches, the canals of Hering and the peribiliary glands, respectively. The complexity of iCCA pathogenesis highlights the need of a multidisciplinary, translational and systemic approach to this malignancy. This review will focus on the advances of iCCA epidemiology, histo-morphology, risk factors, molecular pathogenesis, revealing the existence of multiple subsets of iCCA.

关键词： Cholangiocarcinoma classifications inflammation cells of origin stem cells molecular profiling

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Intraoperative cholangio-ultrasonography(IOCUS)during hepatectomy with resection of the biliary confluence:An effective alternative to intraoperative cholangiography

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 417-420页

作者： Daniele Del Fabbro Fabio Procopio Jacopo Galvanin guido Costa Simone Famularo Angela Palmisano Matteo Donadon guido Torzilli Division of Hepatobiliary Surgery Department of SurgeryIRCCS Humanitas Research HospitalVia A.Manzoni 56Rozzano 20089MilanItaly Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 4Pieve Emanuele 20072MilanItaly

Intraoperative ultrasonography(IOUS)in hepatobiliary surgery is well known as an essential tool for radical and safe hepatectomies,allowing to perform parenchymal sparing surgery and,as consequence,to expand the surgical indications for patients otherwise considered unresectable.Nevertheless,since many years,despite its effectiveness in the study of vascular anatomy of the liver,the gold standard for the assessment of biliary anatomy during surgery is intraoperative cholangiography(IOC),which is used for the validation of preoperative imaging as well as for guiding reconstruction in case of bile duct injury or resection.

关键词： anatomy biliary ultrasonography

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Getting the Most Out of Every Training Day: The Influence of Instructors on Self-Regulated Learning During Firefighter Leadership Courses

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International Journal of Disaster Risk Science 2024年第3期15卷 332-345页

作者： Stefan R?seler Micha Hilbert guido Hertel Meinald T.Thielsch Department of Psychology University of Münster

Leadership courses in the fire services are highly challenging, and they can seriously exhaust trainees and hamper their selfregulated learning efforts(for example, setting goals, focusing attention, seeking feedback). We theorize that experiences of failure or overload can curtail trainees' available energy resources on subsequent training days, which, in turn, should affect trainees' learning efforts. Given instructors' central role in leadership courses, we hypothesize that supportive and humble instructor behaviors decrease experiences of failure and overload and, thus, increase self-regulated learning. Moreover, we argue that supportive instructor behavior may amplify the positive effects of high energy resources, while humble behavior may alleviate the negative impact of low resource levels. We tested preregistered hypotheses with 118 firefighters participating in two-week leadership courses at a German fire academy. The participants completed short web-based questionnaires before and after classes each day. Multilevel analyses confirmed that perceived daily supportive and humble instructor behavior predicted trainees' reports of daily self-regulated learning activity. Notably, this effect was independent from positive effects of trainees' reported energy resources in the morning. Supportive and humble behavior did not moderate the eff ect of energy resources. Our findings suggest that instructors play a crucial role in facilitating effective learning under challenging training conditions. Furthermore, we offer implications for leaders in fire services, who often conduct trainings with their subordinates.

关键词： Diary study Fire services Instructor behavior Leadership training Resource investment

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The formation and growth mechanisms of young back-arc spreading ridges from high-resolution bathymetry:The Marsili Seamount(Tyrrhenian Sea,Italy)

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Geoscience Frontiers 2024年第1期15卷 325-338页

作者： Eugenio Nicotra Salvatore Passaro guido Ventura Dipartimento di Biologia Ecologia e Scienze della Terra Universitàdella Calabria87036 Arcavacata di RendeCosenzaItaly Istituto di Scienze Marine CNR 80133 NapoliItaly Istituto Nazionale di Geofisica e Vulcanologia 00143 RomaItaly Istituto per lo Studio degli impatti Antropici e Sostenibilitáin ambiente marino CNR 91026 Capo GranitolaTrapaniItaly

The formation and growth mechanisms of Mid-Ocean Ridges(MOR)are relatively well known,whereas those of back-arc spreading ridges are comparatively less known because geophysical,geochemical,and morphological data are scarce and of low density.Here we present a high-resolution bathymetry of the Marsili Seamount(MS;1 Ma-3 ka),which represents the inflated spreading ridge of the 2 Ma old Marsili back-arc basin associated to the subduction of the Ionian Sea below the Calabrian Arc and Tyrrhenian Sea.MS is 70 km long,30 km wide,and its height reaches about 3000 m from surrounding seafloor.Our new digital bathymetric model has a 5 m grid cell size resolution and covers the MS bathymetry from-1670 mbsl to the top at-491 mbsl.We conduct morphometric and morphological analyses of the bathymetry and recognize landforms due to volcanic,tectonic,hydrothermal and gravity processes.MS consists of volcanoes related to fissural and central-type activity,this latter located at the northern and southern tips of the main dike swarms.Dike swarms represent the surface expression of different ridge segments whose strikes are controlled by the larger scale back-arc spreading processes and by the local occurrence of an active hydrothermal field.This latter develops in a flat area between two partly overlapping ridge segments where historical volcanism and extensional processes concentrate.Such ridges represent the embryonic stage of the formation of transform-like faults.Central volcanoes,the northern of which is characterized by a caldera,form at the tips of MS because the decrease in width of the major volcanic fissures promotes vent localization associated with the formation of sill-like reservoirs from which central-type vents may develop.Gravity processes affecting the MS flanks are due to shallow seafloor sliding.Caldera collapses affecting the northernmost central-type polygenic volcano must be included in the evaluation of the hazard related to potential tsunami.Inward dipping faults characterize the MS eastern flank suggesting

关键词： Back-arc spreading ridge Morphology Tectonics Volcanism Marsili seamount

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Profiles of the Headspace Volatile Organic and Essential Oil Compounds from the Tunisian Cardaria draba (L.) Desv. and Its Leaf and Stem Epidermal Micromorphology

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Phyton-International Journal of Experimental Botany 2024年第4期93卷 725-744页

作者： Wissal Saadellaoui Samiha Kahlaoui Kheiria Hcini Abir Haddada Noomene Sleimi Roberta Ascrizzi guido Flamini Fethia Harzallah-Skhiri Sondes Stambouli-Essassi Laboratory of Biodiversity Biotechnology and Climate Change(LR11-ES09)Faculty of Sciences of TunisUniversity of Tunis El ManarTunis1060Tunisia Laboratory RME-Resources Materials and EcosystemsFaculty of Sciences of BizerteUniversity of CarthageJarzounaBizerte7021Tunisia Dipartimento di Farmacia Universitàdi PisaVia Bonanno 33Pisa56126Italy Laboratory of Bioresources:Integrative Biology and Valorization(LR14-ES06) High Institute of Biotechnology of MonastirUniversity of MonastirMonastir5000Tunisia

In this work, we investigated aroma volatiles emanated by dry roots, stems, leaves, flowers, and fruits of Cardariadraba (L.) Desv. growing wild in Tunisia and its aerial part essential oils (EOs) composition. A total of 37 volatileorganic compounds (96.7%–98.9%) were identified;4 esters, 4 alcohols, 7 hydrocarbons, 12 aldehydes, 5 ketones,1 lactone, 1 organosulfur compound, 2 organonitrogen compounds, and 1 acid. The hydrocarbons form the maingroup, representing 49.5%–84.6% of the total detected volatiles. The main constituent was 2,2,4,6,6-pentamethylheptane(44.5%–76.2%) reaching the highest relative percentages. Forty-two compounds were determined in thetwo fractions of EOs, representing 98.8% and 97.2% of the total oil composition, respectively. The principal componentswere hexadecanoic acid (34.6%), 6-methyl-5-hepten-2-one (18.3%), decanal (15.0%), 6,10,14-trimethyl-2-pentadecanone (13.2%), and n-pentacosane (13%). Micromorphological details of the leaf and stem epidermisusing light microscopy revealed polygonal cells with sinuous walls in the adaxial and abaxial leaf surfaces andnearly rectangular and long ones with linear and thick walls for the stem epidermis. The stomata complexes wereanisocytic in the leaf epidermis and mainly anisocytic and rarely paracytic in the stem epidermis. Non-glandulartrichomes were unbranched and long with an acute apex or short with a convex apex. The glandular ones wereidentified for the first time in this species. They were short-stalked with a large secretory head. The highest stomatalindex (17.02%) was recorded in the abaxial leaf surface. The identification of headspace volatiles and essentialoil compounds can be used to characterize this species, and the various epidermis micromorphologicalfeatures are very useful for biosystematics taxonomic studies within Brassicaceae.

关键词： Cardaria draba aroma profile essential oils epidermis trichomes

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An Original Didactic about Standard Model (Geometric Model of Particle: The Quarks)

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第2期10卷 854-874页

作者： Giovanni guido Abele Bianchi Gianluigi Filippelli High Scholl “ C. Cavalleri&#8221 Parabiago (Milan) Italy High Scholls “ Gandini&#8221 Lodi Italy INAF Astronomic Observatory “ Brera&#8221 Milan Italy

This work shows a didactic model representative of the quarks described in the Standard Model (SM). In the model, particles are represented by structures corresponding to geometric shapes of coupled quantum oscillators (GMP). From these didactic hypotheses emerges an in-depth phenomenology of particles (quarks) fully compatible with that of SM, showing, besides, that the number of possible quarks is six.

关键词： Golden Particle Quark Sub-Oscillator Semi-Quanta IQuO Geometric Structure Golden Number Massive Coupling Interpenetration IQuO Pion Meson

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