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IN VIVO NEAR-INFRAREDFLUORESCENCEIMAGING OF HUMANCOLONADENOCARCINOMABY SPECIFIC IMMUNOTARGETINGOFA TUMOR-ASSOCIATEDMUCIN

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 407-422页

作者： RALPH S.DACOSTA YING TANG TUULA KALLIOMAKI RAYMOND M.REILLY ROBERT WEERSINK ALISHA R.ELFORD norman E.marcon BRIAN C.WILSON Division of Biophysics and Bioimaging Ontario Cancer Institute 610 University of TorontoTorontoOntarioM5G 2M9Canada Department of Medical Biophysics University of Toronto Princess Margaret Hospital/Ontario Cancer Institute University Health NetworkTorontoOntarioCanada NIH/NCI Radiation Oncology Branch BethesdaMDUSA Division of Clinical Investigation and Human Physiology Toronto General Hospital Research Institute and University of Toronto Leslie Dan Faculty of Pharmacy TorontoOntarioCanada Laboratory for Applied Biophotonics University Health Network TorontoOntarioCanada Campbell Family Institute for Breast Cancer Research University Health Network/Ontario Cancer Institute Department of Medical Biophysics and Immunology Toronto OntarioCanada St.Michael’s Hospital Center for Therapeutic Endoscopy and Endoscopic Oncology Toronto OntarioCanada

Background and Aims: Accurate endoscopic detection of premalignant lesions and earlycancers in the colon is essential for cure, since prognosis is closely related to lesion size andstage. Although it has great clinical potential, autofluorescence endoscopy has limited tumorto-normal tissue image contrast for detecting small preneoplastic lesions. We have developed amolecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate whichtargets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescencebased endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T)subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivowhole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours postinjection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstratedthat modification of CC49 antibodies did not alter their specific tumor-localizing properties, andwas antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probetargeting a tumor-associated mucin detects colonic tumors at the molecular level in real time,and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.

关键词： Autofluorescence imaging endoscopy colon adenocarcinoma TAG72 CC49 mucin monoclonal antibody conjugate confocal fluorescence microscopy.

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Endoscopic diagnosis and treatment of early esophageal squamous neoplasia

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World Journal of Gastrointestinal Endoscopy 2017年第9期9卷 438-447页

作者： Yuto Shimamura Takashi Ikeya norman marcon Jeffrey D Mosko Division of Gastroenterology St.Michael’s HospitalUniversity of Toronto Takashi Ikeya Department of GastroenterologySt.Luke’s International Hospital

Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and *** carries a poor prognosis as more than half of patients present with advanced and unresectable *** contributing factor is the increased risk of lymph node metastases at early stages of *** such,it is essential to detect squamous cell neoplasia (SCN) at an early *** order to risk stratify lesions,endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol's *** assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to *** mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective *** ablation and other endoscopic treatments are currently available although should not be considered first line at this *** objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN.

关键词： Esophageal squamous cell neoplasia Image enhanced endoscopy Esophageal squamous cell carcinoma endoscopic detection Chromoendoscopy Endoscopic mucosal resection Endoscopic submucosal dissection

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Clinical characteristics of young patients with early Barrett’s neoplasia

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World Journal of Gastroenterology 2019年第24期25卷 3069-3078页

作者： Yugo Iwaya Yuto Shimamura Kenichi Goda Enrique Rodríguez de Santiago John Gerard Coneys Jeffrey D Mosko Gabor Kandel Paul Kortan Gary May norman marcon Christopher Teshima Advanced Therapeutic Endoscopy Centre St Michael’s HospitalUniversity of TorontoToronto M5B 1W8OntarioCanada Department of Gastroenterology Dokkyo Medical UniversityTochigi 321-0293Japan Department of Gastroenterology Ramón y Cajal university hospitalMadrid 28034Spain

BACKGROUND Esophageal adenocarcinoma(EAC)and high-grade dysplasia(HGD)may appear in young patients with Barrett's esophagus(BE).However,characteristics of Barrett's-related neoplasia in this younger population remain *** To identify clinical characteristics that differ between young and old patients with early-stage Barrett's-related *** We conducted a retrospective analysis of a prospectively maintained database comprised of consecutive patients with early-stage EAC(pT1)and HGD at a tertiary-referral center between 2001 and *** characteristics,drug and risk factor exposures,clinicopathological staging of EAC/HGD and treatment outcomes[complete eradication of neoplasia(CE-N),complete eradication of intestinal metaplasia(CE-IM),recurrence of neoplasia and recurrence of intestinal metaplasia]were *** analyses were performed to identify factors that differed significantly between older and younger(≤50 years)*** We identified 450 patients with T1 EAC and HGD(74%and 26%,respectively);45(10%)were≤50 *** to the older group,young patients were more likely to present with ongoing gastroesophageal reflux disease(GERD)symptoms(55%vs 38%,P=0.04)and to be obese(body mass index>30,48%vs 32%,P=0.04).Multivariate logistic regression analysis showed that young patients were significantly more likely to have ongoing GERD symptoms[odds ratio(OR)2.00,95%confidence interval(CI)1.04-3.85,P=0.04]and to be obese(OR 2.06,95%CI 1.07-3.98,P=0.03)whereas the young group was less likely to have a smoking history(OR 0.39,95%CI 0.20-0.75,P50 years of age,younger patients should be considered for screening endoscopy if they suffer from obesity and GERD symptoms.

关键词： Barrett's Esophagus Gastroesophageal reflux disease Obesity Esophageal adenocarcinoma High-grade dysplasia Guideline Young patient

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Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.J. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk S.V. Addepalli M.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik M.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot M. Ait Tamlihat B. Aitbenchikh I. Aizenberg M. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt M. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi M. Algren M. Alhroob B. Ali H.M.J. Ali S. Ali S.W. Alibocus M. Aliev G. Alimonti W. Alkakhi C. Allaire B.M.M. Allbrooke J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani M. Alvarez Estevez A. Alvarez Fernandez M. Alves Cardoso M.G. Alviggi M. Aly Y. Amaral Coutinho A. Ambler C. Amelung M. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel M.T. Anthony E. Antipov M. Antonelli F. Anulli M. Aoki T. Aoki J.A. Aparisi Pozo M.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena J-F. Arguin S. Argyropoulos J.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah J. Assahsah K. Assamagan R. Astalos S. Atashi R.J. Atkin M. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia M. Bahmani A.J. Bailey V.R. Bailey J.T. Baines L. Baines O.K. Baker E. Bakos D. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.M. Baldin P. Balek E. Ballabene F. Balli L.M. Baltes W.K. Balunas J. Balz E. Banas M. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak M. Barakat E.L. Barberio D. Barberis M. Barbero M.Z. Barel K.N. Barends T. Barillari M-S. Barisits T. Barklow P. Baron D.A. Baron Mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS JET QUARK GLUON TAGGING

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