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Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma

World Journal of Gastroenterology 2012年第15期18卷 1793-1799页

作者： Jaudah Al-Maghrabi Abdelbaset Buhmeida Eman Emam Kari Syrjnen Abdulrahman Sibiany Mohmmad Al-Qahtani Mahmoud Al-Ahwal Department of Pathology King Abdulaziz UniversityJeddah 21589Saudi Arabia Center of excellence in genomic medicine research King Abdulaziz UniversityJeddah 21589Saudi Arabia Department of Oncology and Radiotherapy Turku University HospitalT-Hospital(Administration)FIN20521 TurkuFinland Department of Surgery King Abdulaziz UniversityJeddah 21589Saudi Arabia Department of medicine Scientific Chair for Colorectal CancerKing Abdulaziz UniversityJeddah 21589Saudi Arabia

AIM:To correlate cyclooxygenase-2(COX-2)expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma(CRC).METHODS:Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94 patients with *** were diagnosed and treatedat the Departments of Surgery and Oncology,King Abdulaziz University Hospital,Saudi ***:Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression,whereas 44%of cases were completely *** were no significant correlations between COX-2 expression and sex,age,grade or tumor ***,COX-2 expression revealed a significant correlation with tumor stage(P=0.01)and distant metastasis(P=0.02),and a borderline association with lymph node involvement(P =0.07).Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression(P<0.009).In univariate Kaplan-Meier survival analysis,there was a significant(P=0.026)difference in disease-free survival between COX-2-positive and negative tumors in favor of the ***-2 expression did not significantly predict disease-specific survival,which was much shorter for COX-2-positive *** multivariate(COX)models,COX-2 did not appear among the independent predictors of disease-free survival or disease-specific ***:COX-2 expression seems to provide useful prognostic information in CRC,while predicting the patients at high risk for recurrent disease.

关键词： Colorectal carcinoma Cyclooxygenase-2 Immunohistochemistry Disease outcome Adjuvant therapy

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From target discovery to clinical drug development with human genetics

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四川生理科学杂志 2023年第9期45卷 1756-1756页

作者： Katerina Trajanoska canada excellence research chair in genomic medicine Department of Human Genetics Faculty of Medicine and Health Sciences Victor Phillip Dahdaleh Institute of Genomic Medicine McGill University Montreal Quebec Canada Lady Davis Institute for Medical research Jewish General Hospital McGill University Montreal Quebec Canada Department of Epidemiology and Biostatistics and Occupational Health McGill University Montreal Quebec Canada

The substantial investments in human genetics and genomics made over the past three decades were anticipated to result in many innovative *** we investigate the extent to which these expectations have been met,excluding cancer *** our search,we identified 40 germline genetic observations that led directly to new targets and subsequently to novel approvedtherapies for 36 rare and 4 common *** median time between genetic target discovery and drug approval was 25 years.

关键词： drug clinical approval

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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Organ-on-a-chip platforms for evaluation of environmental nanoparticle toxicity

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Bioactive Materials 2021年第9期6卷 2801-2819页

作者： Rick Xing Ze Lu Milica Radisic Institute of Biomedical Engineering University of TorontoTorontoONCanada Department of Chemical Engineering and Applied Chemistry University of TorontoTorontoONCanada Toronto General research Institute University Health NetworkTorontoONCanada The Heart and Stroke/Richard Lewar Centre of excellence TorontoONCanada

Despite showing a great promise in the field of nanomedicine,nanoparticles have gained a significant attention from regulatory agencies regarding their possible adverse health effects upon environmental *** those nanoparticles are generated through intentional or unintentional means,the constant exposure to nanomaterials can inevitably lead to unintended consequences based on epidemiological data,yet the current understanding of nanotoxicity is insufficient relative to the rate of their emission in the environment and the lack of predictive platforms that mimic the human *** calls for a development of more physiologically relevant models,which permit the comprehensive and systematic examination of toxic properties of *** the advancement in microfabrication techniques,scientists have shifted their focus on the development of an engineered system that acts as an intermediate between a well-plate system and animal models,known as *** ability of organ-on-a-chip models to recapitulate in vivo like microenvironment and responses offers a new avenue for nanotoxicological *** this review,we aim to provide overview of assessing potential risks of nanoparticle exposure using organ-on-a-chip systems and their potential to delineate biological mechanisms of epidemiological findings.

关键词： Organ-on-a-chip Toxicity Nanoparticles

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Crop adaptation to climate change:An evolutionary perspective

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Molecular Plant 2023年第10期16卷 1518-1546页

作者： Lexuan Gao Michael B.Kantar Dylan Moxley Daniel Ortiz-Barrientos Loren H.Rieseberg CAS Center for excellence in Molecular Plant Sciences Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China Department of Tropical Plant&Soil Sciences University of Hawaii at ManoaHonoluluHIUSA Department of Botany and Biodiversity research Centre University of British ColumbiaVancouverBCCanada School of Biological Sciences and Australian research Council Centre of excellence for Plant Success in Nature and Agriculture The University of QueenslandBrisbaneQLDAustralia

The disciplines of evolutionary biology and plant and animal breeding have been intertwined throughout their development,with responses to artificial selection yielding insights into the action of natural selection and evolutionary biology providing statistical and conceptual guidance for modern *** we offer an evolutionary perspective on a grand challenge of the 21st century:feeding humanity in the face of climate *** first highlight promising strategies currently under way to adapt crops to current and future climate *** include methods to match crop varieties with current and predicted environments and to optimize breeding goals,management practices,and crop microbiomes to enhance yield and sustainable *** also describe the promise of crop wild relatives and recent technological innovations such as speed breeding,genomic selection,and genome editing for improving environmental resilience of existing crop varieties or for developing new ***,we discuss how methods and theory from evolutionary biology can enhance these existing strategies and suggest novel *** focus initially on methods for reconstructing the evolutionary history of crops and their pests and symbionts,because such historical information provides an overall framework for crop-improvement *** then describe how evolutionary approaches can be used to detect and mitigate the accumulation of deleterious mutations in crop genomes,identify alleles and mutations that underlie adaptation(and maladaptation)to agricultural environments,mitigate evolutionary trade-offs,and improve critical *** feedback between the evolution and crop biology communities will ensure optimal design of strategies for adapting crops to climate change.

关键词： abiotic stress resistance climate change crop adaptation Darwinian agriculture evolutionary biology plant breeding

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Does a shift in shade tolerance as suggested by seedling morphology explain differences in regeneration success of northern red oak in native and introduced ranges?

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Journal of Forestry research 2022年第3期33卷 949-962页

作者： Peter Nosko Kerri Moreau Christian Kuehne Kelly C.Major Jürgen Bauhus Department of Biology and Chemistry Nipissing UniversityNorth BayONP1B 8L7Canada chair of Silviculture Freiburg University79085FreiburgGermany Division of Forestry and Forest Resources Norwegian Institute of Bioeconomy ResearchP.O.Box 1151431ÅsNorway Tulloch Engineering 1942 Regent StUnit LSudburyONP3E 5V5Canada

Across North America, forests dominated by Quercus rubra L. (northern red oak), a moderately shade-tolerant tree species, are undergoing successional replacement by shade-tolerant competitors. Under closed canopies, Q. rubra seedlings are unable to compete with these shade-tolerant species and do not recruit to upper forest strata. In Europe, natural regeneration of introduced Q. rubra is often successful despite the absence of fire, which promotes regeneration in the native range. Considering that understorey light availability is a major factor affecting recruitment of seedlings, we hypothesized that Q. rubra seedlings are more shade tolerant in the introduced range than in the native range. Morphological traits and biomass allocation patterns of seedlings indicative of shade tolerance were compared for Q. rubra and three co-occurring native species in two closed-canopy forests in the native range (Ontario, canada) and introduced range (Baden-Württemburg, Germany). In the native range, Q. rubra allocated a greater proportion of biomass to roots, while in the introduced range, growth and allocation patterns favored the development of leaves. Q. rubra seedlings had greater annual increases in height, diameter and biomass in the introduced range. Q. rubra seedlings in the introduced range were also younger;however, they had a mean area per leaf and a total leaf area per seedling that were five times greater than seedlings in the native range. Such differences in morphological traits and allocation patterns support the hypothesis that Q. rubra expresses greater shade tolerance in the introduced range, and that natural regeneration of Q. rubra is not as limited by shade as in the native range. The ability of Q. rubra seedlings to grow faster under closed canopies in Europe may explain the discrepancy in regeneration success of this species in native and introduced ranges. Future research should confirm findings of this study over a greater geographical range in native

关键词： Alien species Cross-continental study Forest regeneration Introduced species Seedling morphology Plant functional traits Quercus rubra

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eTumorMetastasis:A Network-based Algorithm Predicts Clinical Outcomes Using Whole-exome Sequencing Data of Cancer Patients

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genomics, Proteomics & Bioinformatics 2021年第6期19卷 973-985页

作者： Jean-Sébastien Milanese Chabane Tibiche Naif Zaman Jinfeng Zou Pengyong Han Zhigang Meng Andre Nantel Arnaud Droit Edwin Wang Human Health Therapeutics National Research Council CanadaMontreal H4P 2R2Canada genomics Center Centre Hospitalier Universitaire de Québec-UniversitéLaval Research CenterQuebec G1V 4G2Canada Department of Biochemistry&Molecular Biology Medical Geneticsand OncologyUniversity of CalgaryCalgary T2N 4N1Canada Alberta Children’s Hospital research Institute and Arnie Charbonneau Cancer research Institute University of CalgaryCalgary T2N 4N1Canada Institute of Biotechnology Chinese Academy of Agricultural SciencesBeijing 100086China Department of medicine McGill UniversityMontreal H3G 2M1Canada

Continual reduction in sequencing cost is expanding the accessibility of genome sequencing data for routine clinical ***,the lack of methods to construct machine learning-based predictive models using these datasets has become a crucial bottleneck for the application of sequencing technology in ***,we develop a new algorithm,eTumorMetastasis,which transforms tumor functional mutations into network-based profiles and identifies network operational gene(NOG)*** signatures model the tipping point at which a tumor cell shifts from a state that doesn’t favor recurrence to one that *** show that NOG signatures derived from genomic mutations of tumor founding clones(i.e.,the‘most recent common ancestor’of the cells within a tumor)significantly distinguish the recurred and non-recurred breast tumors as well as outperform the most popular genomic test(i.e.,Oncotype DX).These results imply that mutations of the tumor founding clones are associated with tumor recurrence and can be used to predict clinical *** such,predictive tools could be used in clinics to guide treatment ***,the concepts underlying the eTumorMetastasis pave the way for the application of genome sequencing in predictions for other complex genetic *** pseudocode and related data used in this study are available at https://***/WangEdwinLab/eTumorMetastasis.

关键词： Breast cancer Sequencing data Predictive model Systems biology Machine learning

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Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第38期26卷 5759-5783页

作者： Simmone D'souza Keith CK Lau Carla S Coffin Trushar R Patel Department of Microbiology Immunologyand Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgary T2N 1N4ABCanada Department of Chemistry and Biochemistry Alberta RNA Research and Training InstituteUniversity of LethbridgeLethbridge T1K3M4ABCanada

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis,cancer,and liver *** cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver *** tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and *** infection with hepatitis B virus(HBV),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for *** to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of *** mechanisms used by HBV,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways by viral *** integration to promote genome instability is a feature of HBV infection,and metabolic reprogramming leading to steatosis is driven by HCV *** current review aims to provide a brief overview of HBV,HCV and HDV molecular biology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC.

关键词： Chronic viral infection Hallmarks of cancer Hepatocellular carcinoma Hepatitis B virus Hepatitis C virus Hepatitis delta virus co-infection Molecular mechanisms Viral hepatitis

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Plant Evolutionary Adaptation

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Plant Communications 2020年第6期1卷 1-3页

作者： Loren H.Rieseberg Lexuan Gao Department of Botany and Biodiversity research Centre University of British ColumbiaVancouver BC V6T1Z4Canada CAS Center for excellence in Molecular Plant Sciences Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China

In 1973,evolutionary biologist Theodosius Dobzhansky penned a famous essay titled“Nothing in Biology Makes Sense Except in the Light of Evolution”(Dobzhansky,1973).In the essay,he described how many features of biology,such as the adaptive radiations of Drosophila fruit flies and the similarity of embryo development across animal species,are best explained by *** Dobzhansky’s examples largely came from the animal kingdom,evolution is also the chief unifying theory in plant biology,linking molecular,cell,and whole organism-level *** Communications is intended to represent all of the plant sciences,and evolution can provide connections between the diverse studies published in the *** is illustrated by this special issue on Plant Evolutionary Adaptation,in which evolutionary approaches are employed to explain phenomena ranging from the geographic distribution of genomic variation to patterns of plant dispersal to the success of invasive *** we provide background for the topics addressed by these studies and highlight their main conclusions,moving from molecular to organismal-level studies.

关键词： journal linking explain

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The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm

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Journal of Molecular Cell Biology 2023年第10期15卷 39-53页

作者： Matthias Hamdorf Thomas Imhof Ben Bailey-Elkin Janina Betz Sebastian JTheobald Alexander Simonis Veronica Di Cristanziano Lutz Gieselmann Felix Dewald Clara Lehmann Max Augustin Florian Klein Miguel AAlejandre Alcazar Robert Rongisch Mario Fabri Jan Rybniker Heike Goebel Jörg Stetefeld Bent Brachvogel Claus Cursiefen Manuel Koch Felix Bock Cornea Lab Experimental Ophthalmology Department of OphthalmologyFaculty of Medicine and University Hospital Cologne50937 CologneGermany Terasaki Institute for Biomedical Innovation Los AngelesCA 90024USA Center for Biochemistry Faculty of Medicine and University Hospital Cologne50931 CologneGermany Institute for Experimental Dentistry and Oral Musculoskeletal Biology Faculty of Medicine and University Hospital Cologne50931 CologneGermany Department of Microbiology University of ManitobaWinnipeg MB R3B 2E9 ManitobaCanada Department I of Internal medicine Division of Infectious DiseasesFaculty of Medicine and University Hospital Cologne50937 CologneGermany Center for Molecular medicine Cologne University of Cologne50931 CologneGermany Institute of Virology Faculty of Medicine and University Hospital Cologne50935 CologneGermany German Center for Infection research(DZIF) Partner Site Bonn-Cologne50931 CologneGermany Department of Children and Adolescent medicine Faculty of Medicine and University Hospital Cologne50931 CologneGermany Cologne excellence Cluster Stress Responses in Aging-associated Diseases 50931 CologneGermany Institute for Lung Health(ILH) Universities of Gießen and Marburg Lung CentreMember of the German Center for Lung Research35392 GießenGermany Dermatology Faculty of Medicine and University Hospital Cologne50937 CologneGermany Institute of Pathology Faculty of Medicine and University Hospital Cologne50937 CologneGermany Department of Pediatrics and Adolescent medicine Experimental NeonatologyFaculty of Medicine and University Hospital Cologne50931 CologneGermany

The novel coronavirus pandemic,first reported in December 2019,was caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells,which can elicit acute respiratory distress syndrome(ARDS)characterized by the rapid onset of widespread inflammation,the so-called cytokine *** response to viral infections,monocytes are recruited into the lung and subsequently differentiate into dendritic cells(DCs).DCs are critical players in the development of acute lung inflammation that causes ***,we focus on the interaction of a specific SARS-CoV-2 open reading frame protein,ORF8,with *** show that ORF8 binds to DCs,causes pre-maturation of differentiating DCs,and induces the secretion of multiple proinflammatory cytokines by these *** addition,we identified DC-SIGN as a possible interaction partner of ORF8 on *** of ORF8 leads to reduced production of IL-1β,IL-6,IL-12p70,TNF-α,MCP-1(also named CCL2),and IL-10 by ***,a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.

关键词： COVID-19 SARS-CoV-2 ORF8 cytokine storm dendritic cells

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