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Endohepatology:Arrival at the frontier of interventional endosonography

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World Journal of Gastroenterology 2024年第18期30卷 2397-2401页

作者： Shane P Selvanderan eric lam Neal Shahidi Department of Medicine University of British ColumbiaVancouver V6Z 1Y6BCCanada

Endohepatology describes the emerging field where diagnostic and therapeutic endoscopic ultrasound(EUS)are used for the diagnosis and management of liver disease and its *** this editorial we comment on the article by Gadour et *** spectrum of EUS-guided procedures includes liver parenchymal and lesional biopsy,abscess drainage,treatment of focal liver lesions,diagnosis of portal hypertension and management of gastric *** data suggest that the application of EUS to hepatology is technically feasible and safe,heralding the arrival at a new frontier for *** data,specifically randomised trials comparing EUS to interventional radiology techniques,and continued partnership between endoscopy and hepatology are required to see this field establish itself outside expert tertiary centres.

关键词： Cancer Cirrhosis Endoscopy Endoscopic ultrasound Liver disease

Biliary brush cytology:Factors associated with positive yields on biliary brush cytology

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World Journal of Gastroenterology 2008年第4期14卷 569-573页

作者： Nasim Mahmoudi Robert Enns Jack Amar Jaber AlAli eric lam Jennifer Telford St Paul's Hospital University of British ColumbiaVancouver British ColumbiaCanada

AIM: To evaluate the yield of brushing biliary strictures and the factors associated with a positive result in biliary strictures. METHODS: Data on all consecutive patients (01/02 -10/05) who were identified to have a biliary stricture and who underwent biliary brush cytology were collected. The yield of positive biliary brush cytology was evaluated and compared to results with the gold standard for diagnosis (defi ned as either defi nitive surgical histology or clinical course). Additionally,associated factors of positive results including stricture location,gender,age,mass size,length of stricture,and dilatation prior to brushing cytology were assessed. RESULTS: From 199 patients who had brushing cytology samples (10 patients were excluded due to lack of gold standard diagnosis),77 patients had positive brushing cytology (yield 41%). Variables associated with positive cytology brushing on initial endoscopic retrograde cholangiography were age 1.02 (1.00-1.05),mass size > 1 cm 2.22 (1.01-4.89) and length of stricture > 1 cm 3.49 (1.18-10.2). The sensitivity of biliary brushing was 61%,its specifi city 98%,the positive predictive value reached 99%,and the negative predictive value was 57%. CONCLUSION: Our results revealed a 41% positive yield from brushing cytology. The sensitivity of biliary brushing cytology in our center was 61% and the specif icity was 98%. Predictors of positive yield include older age,mass size > 1 cm,and stricture length of > 1 cm.

关键词： Biliary Endoscopic retrograde cholangiopanc reatography Pancreas Gallbladder Ampulla

CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer

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Cancer Communications 2021年第2期41卷 121-139页

作者： Ailin Chen Shijun Wen Fang Liu Zijian Zhang Meiling Liu Yuanzhong Wu Bin He Min Yan Tiebang Kang eric W-F lam Zifeng Wang Quentin Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China Institute of Cancer Stem Cell Dalian Medical UniversityDalianLiaoning 116044P.R.China Department of Surgery and Cancer Imperial College LondonW120NNLondonUK

Background:Overexpression of Aurora-A(AURKA)is a feature of breast cancer and associates with adverse *** selective Aurora-A inhibitor alisertib(MLN8237)has recently demonstrated promising antitumor responses as a single agent in various cancer types but its phase III clinical trial was reported as a failure since MLN8237 did not show an apparent effect in prolonging the survival of ***,identification of potential targets that could enhance the activity of MLN8237 would provide a rationale for drug combination to achieve better therapeutic ***:Here,we conducted a systematic synthetic lethality CRISPR/Cas9 screening of 507 kinases using MLN8237 in breast cancer cells and identified a number of targetable kinases that displayed synthetic lethality interactions with ***,we performed competitive growth assays,colony formation assays,cell viability assays,apoptosis assays,and xenograft murine model to evaluate the synergistic therapeutic effects of Haspin(GSG2)depletion or inhibition with *** mechanistic studies,immunofluorescence was used to detect the state of microtubules and the localization of Aurora-B and mitotic centromere-associated kinesin(MCAK).Results:Among the hits,we observed that Haspin depletion or inhibition marginally inhibited breast cancer cell growth but could substantially enhance the killing effects of *** studies showed that co-treatment with Aurora-A and Haspin inhibitors abolished the recruitment of Aurora-B and mitotic centromere-associated kinesin(MCAK)to centromeres which were associated with excessive microtubule depolymerization,kinetochore-microtubule(KT-MT)attachment failure,and severe mitotic *** further showed that the combination of MLN8237 and the Haspin inhibitor CHR-6494 synergistically reduced breast cancer cell viability and significantly inhibited both in vitro and in vivo tumor ***:These findings establish Haspin as a synthetic lethal targe

关键词： alisertib Aurora-A breast cancer CHR-6494 CRISPR/Cas9 screening haspin kinetochoremicrotubule mitotic centromere-associated kinesin synthetic lethal xenograft

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诺基亚西门子小基站解决方案

电信技术 2012年第S2期 106-107页

作者： eric lam 诺基亚西门子网络公司

介绍了诺基亚西门子通信网络的Flexi Zone解决方案,该解决方案提供了在宏站网络中部署微型小区的方法。

关键词： Flexi Zone 基站 LTE

A truncated hepatitis E virus ORF2 protein expressed in tobacco plastids is immunogenic in mice

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World Journal of Gastroenterology 2006年第2期12卷 306-312页

作者： Yuan-Xiang Zhou Maggie Yuk-Ting Lee James Ming-Him Ng Mee-Len Chye Wing-Kin Yip Sze-Yong Zee eric lam Department of Botany The University of Hong Kong PokfulamRoad Hong Kong China Biotech Center Rutgers University 59 Dudley RoadNew Brunswick NJ 08901-8520 United States

AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.

关键词： Hepatitis E virus E2 Plastid transformation Vaccine Tobacco

Factors associated with incomplete small bowel capsule endoscopy studies

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World Journal of Gastroenterology 2010年第42期16卷 5329-5333页

作者： Mitchell M Lee Andrew Jacques eric lam Ricky Kwok Pardis Lakzadeh Ajit Sandhar Brandon Segal Sigrid Svarta Joanna Law Robert Enns St Paul's Hospital University of British Columbia770-1190 Hornby StreetVancouverBritish Columbia V6Z 2K5Canada

AIM:To identify patient risk factors associated with incomplete small bowel capsule endoscopy(CE) ***:Data from all CE procedures performed at ***'s Hospital in Vancouver,British Columbia,Canada,between December 2001 and June 2008 were collected and analyzed on a retrospective *** collection for complete and incomplete CE study groups included patient demographics as well as a number of potential risk factors for incomplete CE including indication for the procedure,hospitalization,diabetes mellitus with or without end organ damage,limitations in mobility,renal insufficiency,past history of bowel obstruction,abdominal surgery,abdominal radiation therapy and opiate *** factors were analyzed using a univariable and multivariable logistic regression ***:From a total of 535 CE procedures performed,158 were incomplete(29.5%).The univariable analysis showed that CE procedures performed for overt gastrointestinal bleeding(P = 0.002),and for patients with a prior history of abdominal surgery(P = 0.023) or bowel obstruction(P = 0.023) were significantly associated with incomplete CE *** on opiate medications(P = 0.094) as well as hospitalized patients(P = 0.054) were not statistically significant,but did show a trend towards incomplete *** multivariable analysis showed that independent risk factors for an incomplete CE procedure include prior history of bowel obstruction [odds ratios(OR) 2.77,P = 0.02,95% confidence intervals(CI):1.17-6.56] and procedures performed for gastrointestinal bleeding(Occult OR 2.04,P = 0.037,95% CI:1.04-4.02 and Overt OR 2.69,P = 0.002,95% CI:1.44-5.05).Patients with a prior history of abdominal surgery(OR 1.46,P = 0.068,95% CI:0.97-2.19),those taking opiate medications(OR 1.54,P = 0.15,95% CI:0.86-2.76) and hospitalized patients(OR 1.82,P = 0.124,95% CI:0.85-3.93) showed a trend towards statistical ***:We have identified a number of risk factors for incomplete CE procedures

关键词： Capsule Capsule endoscopy Incomplete endoscopy

Identification of factors associated with sedation tolerance in 5000 patients undergoing outpatient colonoscopy:Canadian tertiary center experience

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World Journal of Gastrointestinal Endoscopy 2016年第20期8卷 770-776页

作者： Alexandra Shingina George Ou Oliver Takach Sigrid Svarta Ricky Kwok Jessica Tong Kieran Donaldson eric lam Robert Enns Department of Gastroenterology Faculty of MedicineUniversity of TorontoToronto General Hospital Department of Gastroenterology Faculty of MedicineUniversity of British Columbia Division of Gastroenterology Saint Paul Hospital

AIM To develop a prediction model aimed at identifying patients that may require higher than usual sedation doses during *** A retrospective chart review on 5000 patients who underwent an outpatient colonoscopy at ***'s Hospital from 2009 to 2010 was conducted in order to develop a model for identifying patients who will require increased doses of *** predictor variables including age,gender,endoscopy indication,high sedation requirements during previous endoscopies,difficulty of the procedure,bowel preparation quality,interventions,findings as well as current use of benzodiazepines,opioids and alcohol were *** outcome of study was the use ofhigh dose of sedation agents for the *** particular,the high dose of sedation was defined as fentanyl greater than 50 mcg and midazolam greater than 3 *** Analysis of 5282 patients(mean age 57 ± 12,49% female) was *** common indication for the procedure was screening colonoscopy(57%).Almost half of our patients received doses exceeding Fentanyl 50 mcg and Midazolam 3 *** regression models identified the following variables associated with high sedation:Younger age(OR=0.95 95%CI:0.94-0.95;P lammatory Bowel Disease(OR=1.45,95%CI:1.04-2.03;P=0.02) as indications for the procedure;difficult procedure as defined by gastroenterologist(OR=1.73,95%CI:1.48-2.03;P lammatory bowel disease as an indication(OR=3.17,95%CI:1.58-6.37;P=0.002);difficult procedure as defined by an endoscopist(OR=5.13 95%CI:2.97-8.85;P=0.0001) and current use of opioids,benzodiazepines or antidepressants(OR=2.88,95%CI:1.74-4.77;P=0.001) having the highest predictive value of high sedation require

关键词： Colonoscopy Sedation Sedation tolerance Fentanyl Midazolam Predictive model

Cancer cell employs a microenvironmental neural signal transactivating nucleus-mitochondria coordination to acquire stemness

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3818-3836页

作者： Bin He Rui Gao Shasha Lv Ailin Chen Junxiu Huang Luoxuan Wang Yunxiu Feng Jiesi Feng Bing Liu Jie Lei Bing Deng Bin He Bai Cui Fei Peng Min Yan Zifeng Wang eric W-F lam Bilian Jin Zhiming Shao Yulong Li Jianwei Jiao Xi Wang Quentin Liu State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Medical Oncology The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 510275PR China Institute of Cancer Stem Cell Cancer CenterDalian Medical UniversityDalian 116023PR China Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510080PR China State Key Laboratory of Membrane Biology Peking University School of Life SciencesBeijing 100871PR China Department of Surgery and Cancer Imperial College LondonLondon W120NNUK Department of Breast Surgery Precision Cancer Medicine CenterFudan University Shanghai Cancer CenterShanghai 200032PR China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101PR China

Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains ***,a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element(CRE)transcription factors are convergent activators for cancer *** of transcriptomic profiles,specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE ***,neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis,where ATF1 serves as a conserved *** activation by norepinephrine,ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM,thereby orchestrating nuclear reprograming and mitochondrial ***,single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like *** findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program,suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.

关键词： Cancer neural architectures

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3045-3061页

作者： Jiajun Xie Zifeng Wang Wenjun Fan Youping Liu Fang Liu Xiangbo Wan Meiling Liu Xuan Wang Deshun Zeng Van Wang Bin He Min Yan Zijian Zhang Mengjuan Zhang Zhijie Hou Chunli Wang Zhijie Kang Wenfeng Fang Li Zhang eric W-F lam Xiang Guo Jinsong Yan Yixin Zeng Mingyuan Chen Quentin Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhouChina Institute of Cancer Stem Cell Cancer CenterDalian Medical UniversityDalianChina Department of Hematology Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineLiaoning Medical Center for Hematopoietic Stem Cell TransplantationDalian Key Laboratory of HematologyDiamond Bay Institute of HematologyThe Affiliated Second Hospital of Dalian Medical UniversityDalianChina Department of Radiation Oncology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Sun Yat-sen Institute of Hematology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been *** carci noma(NPC)is a distinctive cancer with poor differe ntiatio n and high prevalenee of Epstein-Barr virus(EBV)***,we show that the expressi on of EBV latent protein LMP1 in duces dediffere ntiated and stem-like status with high plasticity through the transcriptional inhibition of ***,LMP1 upregulates STAT5A and recruits HDAC 1/2 to the CEBPA locus to reduce its histone *** inhibition restored CEBPA expression,reversing cellular dedifferentiation and stem-like status in mouse xeno graft *** fin dings provide a novel mecha nistic epigenetic-based in sight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

关键词： LMP1 cancer plasticity