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Emerging molecular targets and therapy for cholangiocarcinoma

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World Journal of Gastrointestinal Oncology 2017年第7期9卷 268-280页

作者： Hamzeh Kayhanian elizabeth c smyth chiara Braconi Department of Gastrointestinal Oncology Royal Marsden Hospital London and Surrey SM2 5PT Institute of cancer Research London and Surrey SM2 5PT

cholangiocarcinoma(ccA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in ccA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of ccA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. challenges in ccA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for ccA patients.

关键词： cholangiocarcinoma Biliary tract cancer Targeted therapy immunotherapy Mutation Molecular Microenvironment Stroma MiRNA

Role of(～(18)F)2-fluoro-2-deoxyglucose positron emission tomography in upper gastrointestinal malignancies

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World Journal of Gastroenterology 2011年第46期17卷 5059-5074页

作者： elizabeth c smyth Manish A Shah Department of Gastrointestinal Oncology Weill Cornell Medical CollegeMemorial Sloan-Kettering Cancer Center Department of Gastrointestinal Oncology Weill Cornell Medical CollegeNew York-Presbyterian Hospital

The role of whole-body FDG [(～(18)F)2-fluoro-2-deoxy-glucose] positron emission tomography(PET)scan-ning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two ***-PET has demonstrated signifi cant effi cacy in the staging,prognostication and detection of occult metastatic disease in malignancies of the gastrointestinal tract,in addition to assessment of the response to cytotoxic chemotherapy in a more timely manner than has traditionally been possible by more conventional imaging *** sensitivity and specif icity of FDG-PET for the detection and staging of malignancy depend not only on the site and size of the primary tumor and metastases,but also on histologi-cal cell type,reflecting underlying disparities in glucose *** metabolic response to neo-adjuvant chemotherapy or to chemo-radiotherapy in cancers of the gastro-esophageal junction or stomach has been demonstrated in several prospective studies to correlate signifi cantly with both the histological tumor response to treatment and with consequent improvements in overall *** may offer a future paradigm ofpersonalized treatment based on the PET response to ***-PET has been less successful in efforts to screen for and detect recurrent upper gastro-intestinal malignancies,and in the detection of low vol-ume metastatic peritoneal *** to improve the accuracy of PET include the use of novel radiotrac-ers such as(～(18)F)FLT(3-deoxy-3-fluorothymidine)or 11c-choline,or fusion PET-cT with concurrent high-res-olution computed *** review focuses on the role of FDG-PET scanning in staging and response assessment in malignancies of the upper gastrointesti-nal tract,specif ically gastric,esophageal and pancreas carcinoma.

关键词： Positron emission tomography Gastric cancer Esophageal cancer Pancreas cancer

colorectal liver metastases: current management and future perspectives

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World Journal of clinical Oncology 2020年第10期11卷 761-808页

作者： Jack Martin Angelica Petrillo elizabeth c smyth Nadeem Shaida Samir Khwaja HK cheow Adam Duckworth Paula Heister Raaj Praseedom Asif Jah Anita Balakrishnan Simon Harper Siong Liau Vasilis Kosmoliaptsis Emmanuel Huguet Department of Surgery Addenbrookes HospitalNIHR Comprehensive Biomedical Research and Academic Health Sciences CentreCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUnited Kingdom Department of Precision Medicine Division of Medical OncologyUniversity of Campania"L.Vanvitelli"Napoli 80131Italy&Medical Oncology UnitOspedale del Mare80147 Napoli Italy Department of Oncology Addenbrookes HospitalNIHR Comprehensive Biomedical Research and Academic Health Sciences CentreCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUnited Kingdom Department of Radiology Addenbrookes HospitalNIHR Comprehensive Biomedical Research and Academic Health Sciences CentreCambridge University Hospitals NHS Foundation TrustCambridge CB220QQUnited Kingdom Department of Nuclear Medicine Addenbrookes HospitalNIHR Comprehensive Biomedical Research and Academic Health Sciences CentreCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUnited Kingdom Department of Pathology Addenbrookes HospitalNIHR Comprehensive Biomedical Research and Academic Health Sciences CentreCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUnited Kingdom

The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(cRLM)during the course of their *** management of cRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology(cross sectional,nuclear medicine and interventional),Oncology,Liver surgery,colorectal surgery,and *** management is based on assessment of sophisticated clinical,radiological and biomarker *** incomplete evidence in this very heterogeneous patient group,maximising resection of cRLM using all available techniques remains a key objective and provides the best chance of long-term survival and *** this end,liver resection is maximised by the use of downsizing chemotherapy,optimisation of liver remnant by portal vein embolization,associating liver partition and portal vein ligation for staged hepatectomy,and combining resection with ablation,in the context of improvements in the functional assessment of the future remnant *** resection may safely be carried out laparoscopically or open,and synchronously with,or before,colorectal surgery in selected *** unresectable patients,treatment options including systemic chemotherapy,targeted biological agents,intraarterial infusion or bead delivered chemotherapy,tumour ablation,stereotactic radiotherapy,and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to *** evolving areas include biomarker characterisation of tumours,the development of novel systemic agents targeting specific oncogenic pathways,and the potential reemergence of radical surgical options such as liver transplantation.

关键词： colorectal cancer Liver Metastases Management Review

A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan cuccia Rachael coates Blake Nassar Ethan Littlefield elizabeth c.Martin Adam T.Melvin cain Department of chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause *** this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and *** device provides a platform to evaluate the effects of FSS on McF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the *** of the effects of FSS on McF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the McF-7 cell line at a single cell *** understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(Linum L.)

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Oil crop Science 2024年第2期9卷 121-130页

作者： Kenyon J. Nisbett Abida Alokozai Su Hyun elizabeth Ko G. Adam Mott Jason c.L. Browna Department of Biological Sciences University of Toronto ScarboroughTorontoONCanada Department of cell&Systems Biology University of TorontoTorontoONCanada centre for the Analysis of Genome Evolution&Function University of TorontoTorontoONCanada

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 *** proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple *** differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular *** present study evaluated this hypothesis using annual and perennial flax(Linum L.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar H2O2spraying)and complete prolonged *** chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our *** predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to *** levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using *** chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as *** plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,ch

关键词： Ageing Life history Maximum lifespan Oxidative stress Somatic maintenance

Habitable Land Will Soon Become the World’s Scarcest Resource: Why Appalachia Should choose climate change Havens over Millionaire Estates and Golf courses

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Journal of Environmental Protection 2024年第6期15卷 716-730页

作者： elizabeth c. Hirschman Devonte Booth Tzu-Wei Huang Kamryn Livingston Kobe McReynolds Rachel Six Logan Smith Olivia Toomer Department of Business and Economics University of Virginia-Wise Wise USA

This research advocates for the construction of climate change Haven communities across the Appalachian Region. The proposed development plan can be extended to the northern tier states across the US and also to the northern and mountainous regions of Europe and Asia. We present an analogy to the earlier climate change period of the Last Glacial Maximum/“Ice Age” in which these same northern regions of the planet were covered in ice sheets making them uninhabitable for most humans and many plant and animal species. In some significant ways, the Ice Age scenario can be a reverse-model for our current climate crisis. We also advocate strongly for the prevention of upscale real estate development projects in these same regions of the globe, as these will foreclose the possibility of safely sheltering the millions of persons who will be displaced by climate change over the next 5 to 10 years.

关键词： climate change Appalachia Habitable Land climate change Haven communities Two-caste Economic System Migration Ice Age Analogies

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia Galea Kirsten Holte caroline Luszawski elizabeth Jenkins Jennifer O’Neil carolyn A Emery Rebekah Mannix Kathryn Schneider Keith Owen Yeates Roger Zemek children’s Hospital of Eastern Ontario Research Institute OttawaON K1H 8L1Canada The centre for Health Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury Prevention Research centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta children’s Hospital Research Institute University of calgary CalgaryAB T2N 1N4Canada Hotchkiss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of Psychology University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada School of Rehabilitation Sciences University of OttawaOttawaON K1H 8M5Canada Bruyere Research Institute OttawaON K1N 5C8Canada Departments of Pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA Departments of Pediatrics and Emergency Medicine University of OttawaOttawaON K1H 8M5Canada

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RcTs)of non-pharmacological interventions following ***:We searched MEDLINE,Embase,PsycInfo,cINAHL,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),consensus on Exercise Reporting Template(cERT),and international consensus on Therapeutic Exercise aNd Training(i-cONTENT)*** information was sought my study authors where reporting was *** of bias(ROB)was assessed with the cochrane ROB-2 *** examining non-pharmacological interventions following ***:We included 89 RcTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck *** scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),cERT 17/19(89%;IQR=2;range:10-19),and i-cONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),cERT 24%(5/21),and i-cONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and cERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;cERT:r_(s)=-0.44;p=0.06;i-cONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;cERT:rs=0.04;p=0.86;i-cONTENT:rs=0.12;p=0.60).conclusion:RcTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified *** completeness improved after TIDieR and cERT publication,but p

关键词： concussion Intervention Randomized controlled trial Systematic review

Social and Economic considerations for creating Sustainable climate change Haven communities

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Journal of Environmental Protection 2024年第1期15卷 76-93页

作者： elizabeth c. Hirschman William Bourgin Angel castilla caitlin Glover caitlyn Justice Manuel Munoz Braydon Thompson Justin Snider Olivia Toomer Department of Business and Economics University of Virginia-Wise Wise USA

As climate change Haven communities are constructed across the Northern Hemisphere, it will be necessary to attract two types of migrants to populate them. The first group consists of professionals and companies in eco-sustainable businesses, such as law firms, insurance companies, investment firms, banking, technological innovation, mass media, medical research and pharmaceutical research. The second group will consist of persons engaged in organic/eco-sustainable agriculture whose crops and animal husbandry practices can be transferred successfully to climate change Haven regions. The present research focuses on the social and economic variables that must be taken into account to insure that each new climate change Haven community becomes successfully integrated with the local population and forms a cohesive, harmonious social structure. Examples are given from the United States, France, Spain, Portugal and Italy.

关键词： climate change Haven community Sustainability Organic/Eco Farming Internal Migration Social Integration

Efficacy of Yisui granule(益髓颗粒)on myelodysplastic syndromes in SKM-1 mouse xenograft model through suppressing Wnt/β-catenin signaling pathway

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Journal of Traditional chinese Medicine 2024年第1期44卷 78-87页

作者： WU Jieya HOU Li ZHANG Xiaoyuan elizabeth Gullen GAO chong WANG Jing Department of Oncology and Hematology Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Department of Pharmacology Yale Medical SchoolNew HavenCT 06510USA Department of Oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

OBJEcTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin *** amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein ***:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long ***,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s ***,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin ***:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.

关键词： myelodysplastic syndromes Wnt signaling pathway beta catenin decitabine survival adverse effects sFRP5 gene methylation Yisui granule