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Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond

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World journal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： Emily M Lin jun Gong samuel j klempner joseph Chao Department of Internal Medicine Harbor-UCLA Medical CenterTorranceCA 90509United States Department of Medical Oncology and Developmental Therapeutics City of Hope Comprehensive Cancer CenterDuarteCA 91010United States The Angeles Clinic and Research Institute Los AngelesCA 90404United States samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States

Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEj) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEj cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEj cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEj cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEj cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEj cancer.

关键词： Immunotherapy programmed cell death 1 programmed death ligand 1 microsatellite instablility Gastric cancer

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Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

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World journal of Gastrointestinal Oncology 2022年第2期14卷 511-524页

作者： Lauren Midthun Sungjin Kim Andrew Hendifar Arsen Osipov samuel j klempner joseph Chao May Cho Michelle Guan Veronica R Placencio-Hickok Alexandra Gangi Miguel Burch De-Chen Lin Kevin Waters Katelyn Atkins Mitchell Kamrava jun Gong Department of Medicine Division of Hematology and OncologyCedars-Sinai Medical CenterLos AngelesCA 90048United States Biostatistics and Bioinformatics Research Center Cedars Sinai Medical CenterLos AngelesCA 90048United States samuel Oschin Cancer Center Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Beth Israel Deaconess Medical Center/Harvard Medical SchoolBrigham and Women's Hospital/Harvard Medical SchoolBostonMA 02114United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaIrvineCA 92697United States Department of Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Pathology and Laboratory Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal ***,not all patients with metastatic disease receive *** To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and *** We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without *** A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving *** median follow-up was 69.45 *** median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no *** of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving *** the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on ***,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic

关键词： Esophageal cancer Metastatic Chemotherapy Predictors Survival

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Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

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World journal of Gastrointestinal Surgery 2020年第9期12卷 377-389页

作者： Sungjin Kim Timothy P DiPeri Michelle Guan Veronica R Placencio-Hickok Haesoo Kim jar-Yee Liu Andrew Hendifar samuel j klempner Ryan Nipp Alexandra Gangi Miguel Burch Kevin Waters May Cho joseph Chao Katelyn Atkins Mitchell Kamrava Richard Tuli jun Gong Biostatistics and Bioinformatics Research Center Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Surgical Oncology Department of SurgerySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Division of Hematology and OncologySamuel Oschin Comprehensive Cancer InstituteCedars Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonMA 02114United States Department of Pathology and Laboratory Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor *** all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are *** To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving *** The National Cancer Database was used to identify patients between *** with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were *** with unknown chemotherapy,RT,or nonprimary surgery status were ***-Meier estimates of OS were *** proportional hazards regression models were employed to examine factors influencing *** Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete *** age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic *** majority(72.7%)did not receive other palliative *** both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased *** histologic grade and T-stage were also as

关键词： Esophageal cancer Metastatic Palliative Chemotherapy Radiotherapy Survival

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Single-atom Pt on carbon nanotubes for selective electrocatalysis

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Carbon Energy 2024年第1期6卷 63-71页

作者： samuel S.Hardisty Xiaoqian Lin Anthony R.j.Kucernak David Zitoun Department of Chemistry Bar Ilan Institute of Nanotechnology and Advanced Materials(BINA)Bar Ilan UniversityRamat GanIsrael Department of Chemistry Molecular Science Research HubImperial College LondonLondonUK

Utilizing supported single atoms as catalysts presents an opportunity to reduce the usage of critical raw materials such as platinum,which are essential for electrochemical reactions such as hydrogen oxidation reaction(HOR).Herein,we describe the synthesis of a Pt single electrocatalyst inside single-walled carbon nanotubes(SWCNTs)via a redox *** via electron microscopy,X-ray photoelectron microscopy,and X-ray absorption spectroscopy show the single-atom nature of the *** electrochemical behavior of the sample to hydrogen and oxygen was investigated using the advanced floating electrode technique,which minimizes mass transport limitations and gives a thorough insight into the activity of the *** single-atom samples showed higher HOR activity than state-of-the-art 30%Pt/C while almost no oxygen reduction reaction activity in the proton exchange membrane fuel cell operating *** selective activity toward HOR arose as the main fingerprint of the catalyst confinement in the SWCNTs.

关键词： confinement electrocatalysis hydrogen platinum single atom catalysts

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Constrained re-calibration of two-equation Reynolds-averaged Navier–Stokes models

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Theoretical & Applied Mechanics Letters 2024年第2期14卷 82-89页

作者： Yuanwei Bin Xiaohan Hu jiaqi Li samuel j.Grauer Xiang I.A.Yang Department of Mechanical Engineering Pennsylvania State UniversityUniversity ParkPA 16802USA State Key Laboratory for Turbulence and Complex Systems Peking UniversityBeijing 100871China College of Engineering Peking UniversityBeijing 100871China

Machine-learned augmentations to turbulence models can be advantageous for flows within the training dataset but can often cause harm *** lack of generalizability arises because the constants(as well as the functions)in a Reynolds-averaged Navier–Stokes(RANS)model are coupled,and un-constrained re-calibration of these constants(and functions)can disrupt the calibrations of the baseline model,the preservation of which is critical to the model's *** safeguard the behaviors of the baseline model beyond the training dataset,machine learning must be constrained such that basic calibrations like the law of the wall are kept *** letter aims to identify such constraints in two-equation RANS models so that future machine learning work can be performed without violating these *** demonstrate that the identified constraints are not ***,they help preserve the generalizability of the baseline model.

关键词： Machine learning Turbulence modeling Reynolds-averaged Navier-Stokes

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Sustainable plasticulture in Chinese agriculture: a review of challenges and routes to achieving long-term food and ecosecurity

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Frontiers of Agricultural Science and Engineering 2024年第1期11卷 155-168页

作者： samuel j.CUSWORTH William j.DAVIES Martin R.MCAINSH Carly j.STEVENS Weilu WANG Lancaster Environment Centre Lancaster UniversityLancasterLA14YQUK The Institutes of Agricultural Science and Technology Development Yangzhou UniversityYangzhou 225009China

Plastic pollution is global concern, affecting most aspects of global food production systems. Plasticulture, a practice used in agriculture to improve crop quality and quantity, among other factors, is a significant source of plastic pollution. This review examines the extent of plasticulture in China, the implications of the practice across decades of use and the legislative instruments used to resolve those issues. It briefly assesses the effectiveness of these policies and proposes possible future innovations to promote increases in long-term food and eco-security, where sustainable plasticulture is a key agent for change. While plasticulture has increased agricultural productivity in growth-limiting conditions, plastic pollution in agricultural soils has become acute in China. Consequently, plastic pollution is having deleterious effects on soil health and in turn, crop productivity in China. Plastic pollution in agriculture is a multifaceted issue and so proposed solutions should be informed by this complexity. Current measures do not reflect a holistic approach to solving this socioecological challenge and adopt a top-down approach, with little or no supportive mechanisms. Future recommendations need to consider the particular set of conditions that influence the production, use and end-of-life management of agriplastics,specific to the environmental, economic and social conditions in each location.

关键词： Circular plastics economy crop production food security plastic pollution sustainable plasticulture

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Thermochemical co-conversion of biomass-plastic waste to biochar:a review

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Green Chemical Engineering 2024年第1期5卷 31-49页

作者： Adewale George Adeniyi Kingsley O.Iwuozor Ebuka Chizitere Emenike Oluwaseun j.Ajala samuel Ogunniyi Kabir B.Muritala Department of Chemical Engineering Faculty of Engineering and TechnologyUniversity of IlorinIlorinP.M.B.1515Nigeria Department of Chemical Engineering Landmark UniversityOmu-AranKwara StateP.M.B.1001Nigeria Department of Pure and Industrial Chemistry Nnamdi Azikiwe UniversityAwkaP.M.B.5025Nigeria Department of Chemistry Federal University of TechnologyBosso CampusMinnaNiger StateP.M.B.65Nigeria

Biomass and plastics are two of the most common municipal solid wastes globally that have continuously placed a burden on the *** is therefore important that they are properly *** coconversion offers a valuable opportunity to recycle biomass and plastics simultaneously into biochar,which reduces the time and cost of recycling them individually while producing a material with a wide range of *** study is a review of published literature that discusses the thermochemical co-processing of biomass and plastic wastes into *** was observed that co-pyrolysis and co-hydrothermal carbonization are the most commonly utilized technologies for this *** characteristics of different biomass and plastics that have been thermochemically converted into biochar were *** properties of the resulting biochar are affected by the feedstock composition,pre-treatment and blending ratio,the reactor’s configuration,reaction temperature,and the presence of a *** studies found that treating the feedstocks separately resulted in a lower yield of biochar than processing them *** biochar created by this procedure has been used as a soil additive and as an adsorbent for water *** perspectives and suggestions,such as the necessity for some technical advancement,biochar’s economic benefits,improved government participation,and raised social awareness,were also *** factors have the potential to propel this field of study to great horizons.

关键词： Biomass Co-pyrolysis Plastic Thermochemical process Valorization

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Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

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Oncology Research 2024年第7期32卷 1163-1172页

作者： LISANNE K.A.NEIjENHUIS LEUTA L.NAUMANN SONIA A.M.FERKEL samuel j.S.RUBIN STEPHAN ROGALLA Division of Gastroenterology and Hepatology Department of MedicineSchool of MedicineStanford UniversityStanford94305USA Department of Surgery Leiden University Medical CenterLeiden2333 ZAThe Netherlands Centre for Human Drug Research Leiden2333 CLThe Netherlands Department of General VisceralVascular and Thoracic SurgeryCharite University Medicine BerlinBerlin10117Germany

Background:Osteosarcoma is the most common malignant primary bone *** prognosis for patients with disseminated disease remains very poor despite recent advancements in ***,current treatment regimens bear a signiﬁcant risk of serious side ***,there is an unmet clinical need for effective therapies with improved safety proﬁ*** is an antibacterial agent that has been shown to induce cell death in different types of cancer cell ***:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day *** were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal ***:After 35 days,mice were euthanized,and the tumors were harvested for *** mice were excluded from the analysis due to *** weight was signiﬁcantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this *** tumor weight was signiﬁcantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the *** antineoplastic effects were observed on intramuscular tumors or for intravenous administration of *** were no signiﬁcant differences in microvessel density or mitotic rate between treatment *** body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is ***:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are ***,its toxic proﬁle grants further *** these observations,further research is necessary to

关键词： Osteosarcoma Taurolidine Cancer treatment Chemotherapy Murine models

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Exertional calf pain at kilometer five - Finding the cause

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Sports Medicine and Health Science 2024年第1期6卷 89-93页

作者： samuel A.Renier Angela M.Voight Emilee j.Trost William O.Roberts St.john's Hospital Family Medicine Residency Department of Family Medicine and Community HealthUniversity of Minnesota Medical SchoolMinneapolisMNUSA Summit Orthopedics Woodbury Clinic2090 Woodwinds Dr.WoodburyMN55125USA Minnesota Distance Elite 4007Forest RdMinneapolisMN55416USA Department of Family Medicine and Community Health University of Minnesota Medical School516 Delaware St.SE6-240 Phillips-Wangensteen BuildingMinneapolisMN55455USA

A 23-year-old professional distance runner with several years of exertional calf pain was diagnosed with a unique mixed type III and functional popliteal artery entrapment syndrome(PAES).Surgical reduction of the obstructing tissue allowed her to return to professional *** case highlights the importance of including PAES in the differential for chronic intermittent lower extremity claudication and outlines the work-up required to diagnose this vascular obstruction in younger athletes.

关键词： Claudication Lower leg pain Vascular imaging PAES FPAES Popliteal entrapment

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K jacobs Steven D Morley Kay samuel Katie Morgan Lyndsey Boswell Timothy j Kendall David A Dorward jonathan A Fallowfield Peter C Hayes john N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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