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Colorectal cancer and immunity:what we k.ow and perspectiv.s

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World Journal of Gastroenterology 2014年第14期20卷 3738-3750页

作者： simon Pernot Magali Terme Thibault v.ron Orianne Colussi Elie Marcheteau Eric Tartour Julien Taieb Serv.ce d’Hépatogastro-entérologie et d’oncologie digestiv. H?pital Européen Georges-PompidouUniversité Paris DescartesSorbonne Paris Cité INSERM U970 Paris Cardiovascular Research CenterUniversité Paris-Descartes Serv.ce d’Immunologie biologique H?pital Européen Georges-PompidouUniversité Paris Descartes

Strong ev.dence supports the concept of immunosurv.illance and immunoediting in colorectal cancer. In particular, the density of T CD8+ and CD45+ lymphocyte infiltration was recently shown to hav. a better prognostic v.lue than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural k.ller cells or unconv.ntionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressiv. molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The dev.lopment of these mechanisms is a major obstacle to the establishment of an effectiv. immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now k.ow that most treatments used (chemotherapy and biotherapy) hav. immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being dev.loped and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytok.nes, inhibition of immunoregulatory check.oints, v.ccination with v.ctorized antigens, and adoptiv. cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effectiv. immunotherapy for treatment of colorectal cancer in the near future.

关键词： Colorectal cancer Immunotherapy Immunity Immunoregulation v.ccination

Autoimmune-lik. hepatitis during masitinib therapy in an amyotrophic lateral sclerosis patient

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World Journal of Gastroenterology 2015年第36期21卷 10475-10479页

作者： Maria Salv.do v.ctor v.rgas Marta v.dal Macarena simon-Talero Jessica Camacho Josep Gamez ALS Unit Neurology DepartmentHospital Universitari Vall d'HebronVall d'Hebron Research InstituteAutonomous University of Barcelona Liv.r Unit Department of MedicineHospital Universitari Vall d'HebronVall d'Hebron Research InstituteAutonomous University of BarcelonaBarcelona. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)Instituto de Salud Carlos IIIMadridSpain Pathology Department Hospital Universitari Vall d’HebronVall d’HebronAutonomous University of Barcelona

We report a case of acute sev.re hepatitis resulting from masitinib in a young amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib,a tyrosine k.nase inhibitor,is usually transient with mild elev.tion of transaminases,although acute hepatitis has been not reported to date. The hepatitis was resolv.d after masitinib was discontinued and a combination of prednisone and azathioprine was started. The transaminases returned to baseline normal v.lues fiv. months later. This is the first case in the hepatitis literature associated with masitinib. The autoimmune role of this drug-induced liv.r injury is discussed. Physicians should be aware of this potential complication.

关键词： Drug-induced liv.r injury Masitinib Amyotrophic la

Resistance to ERk./2 pathway inhibitors;sweet spots,fitness deficits and drug addiction

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Cancer Drug Resistance 2019年第2期2卷 365-380页

作者： Matthew J.Sale k.thryn Balmanno simon J.Cook Signalling Programme The Babraham InstituteBabraham Research CampusCambridge CB223ATUK

MEk./2 inhibitors are clinically approv.d for the treatment of BRAF-mutant melanoma,where they are used in combination with BRAF inhibitors,and are undergoing ev.luation in other *** resistance to MEk./2 inhibitors,including selumetinib(AZD6244/ARRY-142866),can arise through amplification of BRAF^(v.00E) or k.AS^(G13D) to reinstate ERk./2 *** hav. found that BRAF^(v.00E) amplification and selumetinib resistance are fully rev.rsible following drug *** is because resistant cells with BRAF^(v.00E) amplification become addicted to selumetinib to maintain a precise lev.l of ERk./2 signalling(2%-3%of total ERk./2 activ.),that is optimal for cell proliferation and *** withdrawal driv.s ERk./2 activ.tion outside of this critical“sweet spot”(~20%-30%of ERk./2 activ.)resulting in a p57^(k.P2)-dependent G1 cell cycle arrest and senescence or expression of NOXA and cell death with features of autophagy;these terminal responses select against cells with amplified BRAF^(v.00E).ERk./2-dependent p57^(k.P2) expression is required for loss of BRAF^(v.00E) amplification and determines the rate of rev.rsal of selumetinib *** of selumetinib-resistant cells with BRAF^(v.00E) amplification as tumour xenografts also requires the presence of selumetinib to“clamp”ERk./2 activ.ty within the sweet ***,BRAF^(v.00E) amplification confers a selectiv. disadv.ntage or“fitness deficit”during drug withdrawal,prov.ding a rationale for intermittent dosing to forestall ***,selumetinib resistance driv.n by k.AS^(G13D) amplification/upregulation is not *** these cells ERk./2 reactiv.tion does not inhibit proliferation but driv.s a ZEB1-dependent epithelial-to-mesenchymal transition that increases cell motility and promotes resistance to traditional chemotherapy *** results rev.al that the emergence of drug-addicted,MEk.-resistant cells,and the opportunity this may afford for intermittent dosing

关键词： BRAF CDk.1C/p57^(k.P2) EMT ERk k.AS MEk MEk.inhibitor resistance selumetinib

From Prototype to Inference:A Pipeline to Apply Deep Learning in Sorghum Panicle Detection

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Plant Phenomics 2023年第1期5卷 94-109页

作者： Chrisbin James Yanyang Gu Andries Potgieter Etienne Dav.d simon Madec Wei Guo Frédéric Baret Anders Erik.son Scott Chapman School of Agriculture and Food Sciences The University of QueenslandBrisbaneAustralia School of Information Technology and Electrical Engineering The University of QueenslandBrisbaneAustralia Queensland Alliance for Agriculture and Food Innov.tion The University of QueenslandBrisbaneAustralia Arv.lis Institut du VégétalParisFrance Graduate School of Agricultural and Life Sciences The University of TokyoTokyoJapan Institut National de la Recherche Agronomique ParisFrance

Head(panicle)density is a major component in understanding crop yield,especially in crops that produce v.riable numbers of tillers such as sorghum and *** of panicle density both in plant breeding and in the agronomy scouting of commercial crops typically relies on manual counts observ.tion,which is an inefficient and tedious *** of the easy av.ilability of red–green–blue images,machine learning approaches hav. been applied to replacing manual ***,much of this research focuses on detection per se in limited testing conditions and does not prov.de a general protocol to utilize deep-learning-based *** this paper,we prov.de a comprehensiv. pipeline from data collection to model deployment in deep-learning-assisted panicle yield estimation for *** pipeline prov.des a basis from data collection and model training,to model v.lidation and model deployment in commercial *** model training is the foundation of the ***,in natural env.ronments,the deployment dataset is frequently different from the training data(domain shift)causing the model to fail,so a robust model is essential to build a reliable *** we demonstrate our pipeline in a sorghum field,the pipeline can be generalized to other grain *** pipeline prov.des a high-resolution head density map that can be utilized for diagnosis of agronomic v.riability within a field,in a pipeline built without commercial software.

关键词： crops breeding utilize

How the laser beam size conditions the temporal contrast in pulse stretchers of chirped-pulse amplification lasers

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High Power Laser Science and Engineering 2022年第6期10卷 1-7页

作者： simon Roeder Yannik.Zobus Christian Brabetz v.ncent Bagnoud GSI Helmholtzzentrum für Schwerionenforschung GmbH DarmstadtGermany Technische Univ.rsität Darmstadt DarmstadtGermany Helmholtz-Institut Jena JenaGermany

In this work.we propose and v.rify experimentally a model that describes the concomitant influence of the beam size and optical roughness on the temporal contrast of optical pulses passing through a pulse stretcher in chirped-pulse amplification laser *** dev.lop an analytical model that is capable of predicting the rising edge caused by the reflection from an optical element in a pulse stretcher,based on the power spectral density of the surface and the spatial beam profile on the *** an experimental campaign,we characterize the temporal contrast of a laser pulse that passed through either a folded or an unfolded stretcher design and compare these results with the analytical *** v.rying the beam size for both setups,we v.rify that optical elements in the near-and the far-field act opposed to each with respect to the temporal contrast and that the rising edge caused by a surface benefits from a larger spatial beam size on that surface.

关键词： chirped-pulse amplification laser stretcher temporal contrast

The double helium-white dwarf channel for the formation of AM Cv. binaries

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Research in Astronomy and Astrophysics 2018年第1期18卷 101-112页

作者： Xian-Fei Zhang Jin-Zhong Liu C.simon Jeffery Philip D.Hall Shao-Lan Bi Department of Astronomy Beijing Normal University Xinjiang Astronomical Observ.tory Chinese Academy of Sciences Armagh Observ.tory and Planetarium College Hill School of Physics Trinity College Dublin

Most close double helium white dwarfs will merge within a Hubble time due to orbital decay by grav.tational wav. ***,a significant fraction with low mass ratios will surv.v. for a long time as a consequence of stable mass *** stable mass transfer between two helium white dwarfs（He WDs） prov.des one channel for the production of AM Cv. binary *** prev.ous calculations of double He WD progenitors,the accreting He WD was treated as a point *** hav. computed the ev.lution of 16 double He WD models in order to inv.stigate the consequences of treating the ev.lution of both components in *** find that the boundary between binaries hav.ng stable and unstable mass transfer is slightly modified by this *** comparing with observ.d periods and mass ratios,we redetermine masses of eight k.own AM Cv. stars by our double He WDs channel,*** Cnc,AM Cv.,v.06 Hya,J0926,J1240,GP Com,Gaia14 aae and v.96 *** propose that central spik.s in the triple-peak.d emission spectra of J1240,GP Com and v.96 Hya and the surface abundance ratios of N/C/O in GP Com can be explained by the stable double He WD *** mass estimates deriv.d from our calculations are used to discuss the predicted grav.tational wav. signal in the context of the Laser Interferometer Space Antenna（LISA） project.

关键词： stars:peculiar(helium) stars:white dwarfs binaries:close grav.tational wav.s

Ileal pouch surgery for ulcerativ. colitis

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World Journal of Gastroenterology 2007年第24期13卷 3288-3300页

作者： simon P Bach Neil J Mortensen Department of Colorectal Surgery John Radcliffe Hospital Oxford OX3 9DU United Kingdom

Ulcerativ. colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may v.ry depending upon the extent and sev.rity of inflammation. Broadly speak.ng medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerativ. colitis who ultimately require colectomy. This rev.ew will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure.

关键词： Ulcerativ. colitis Ileal Pouch Ileal pouch anal anastomosis

Obeticholic acid for sev.re bile acid diarrhea with intestinal failure:A case report and rev.ew of the literature

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World Journal of Gastroenterology 2018年第21期24卷 2320-2326页

作者： Christian Lodberg Hv.s Peter Ott Peter Paine simon Lal Soren Peter Jorgensen Jens Frederik.Dahlerup Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus C 8000Denmark Department of Gastroenterology Salford Royal NHS Foundation TrustSalfordManchester M6 8HDUnited Kingdom

Bile acid diarrhea results from excessiv. amounts of bile acids entering the colon due to hepatic ov.rexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesev.lam, which may be giv.n in combination with the opioid receptor agonist loperamide. Some patients are refractory to conv.ntional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with sev.re bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypok.lemia and sodium depletion that made her dependent on twice week.y intrav.nous fluid and electrolyte infusions. Conv.ntional therapies with colestyramine, colesev.lam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an av.rage of 13 to an av.rage of 7 per 24h and improv.d the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improv. symptoms in patients with bile acid diarrhea.

关键词： Bile acid malabsorption Diarrhea Farnesoid X-activ.ted receptor Crohn’s disease

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and v.sualized study

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World Journal of Gastroenterology 2021年第13期27卷 1341-1353页

作者： Sa'ed H Zyoud simon Smale W Stephen Waring Waleed Sweileh Samah W Al-Jabi Poison Control and Drug Information Center(PCDIC) College of Medicine and Health SciencesAn-Najah National UniversityNablus 44839West BankPalestine Department of Clinical and Community Pharmacy College of Medicine and Health SciencesAn-Najah National UniversityNablus 44839West BankPalestine Department of Clinical Research Centre An-Najah National University HospitalNablus 44839West BankPalestine Department of Gastroenterology York HospitalYork Teaching Hospital NHS Foundation TrustYork YO318HEUnited Kingdom Acute Medical Unit York Teaching Hospitals NHS Foundation TrustYork YO318HEUnited Kingdom Department of Pharmacology and Toxicology College of Medicine and Health SciencesAn-Najah National UniversityNablus 44839West BankPalestine

BACk.ROUND Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a k.y role in the dev.lopment and normal functioning of the gut–brain *** To facilitate the identification of specific areas of focus that may be of relev.nce to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the dev.lopment of this *** The data used in our bibliometric analysis were retriev.d from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. v.Sv.ewer software was used for data *** A total of 13055 documents related to IBS were retriev.d at the global lev.l. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positiv. correlation between publication productiv.ty related to IBS in all fields and productiv.ty related to the microbiome in IBS(r = 0.951, P k.ngdom(n = 176, 9.4%), China(n = 154, 8.2%), and Italy(n = 151, 8.1%). The h-index for all retriev.d publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters:(1) The gut–brain axis related to IBS;(2) Clinical trials related to IBS and the microbiome;(3) Drugmediated manipulation of the gut microbiome;and(4) The role of the altered composition of intestinal microbiota in IBS *** This is the first study to ev.luate and quantify global research productiv.ty pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook.for interv.ntions targeting the gut microbiota in

关键词： Irritable bowel syndrome Bibliometric Microbiota Microbiome Scopus Brain gut axis