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Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer

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Gastroenterology Report 2020年第6期8卷 411-424,I0001页

作者： Anita Lavery Richard C.Turkington Patrick G Johnston centre for cancer research Queen’s University BelfastBelfastUK

Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death *** the setting of resectable disease,there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved ***,only 15%-30%of patients obtain a histopathological response to neoadjuvant therapy,often at the expense of significant *** are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve *** this review,we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this *** place these issues in the wider context of recommendations for biomarker development and *** majority of studies focus on messenger RNA(mRNA)and microRNA(miRNA)*** studies report a range of different genes involved in a wide variety of pathways and biological processes,and this is explained to a large extent by the different platforms and analysis methods *** studies are also vastly underpowered so are not suitable for identifying a candidate *** molecular subtypes of oesophageal cancer have been proposed,although little is known about how these relate to clinical *** anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.

关键词： oesophageal cancer predictive biomarkers chemotherapy radiotherapy gene expression pathological response

Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma(MM)

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Journal of cancer Metastasis and Treatment 2022年第1期8卷 302-316页

作者： Reena R.D'Souza Paraskevi Dimou Reyisa Bughda Elizabeth Hawkins Clara Leboreiro Babe Astero Klampatsa Division of cancer Therapeutics The Institute of Cancer ResearchLondon SM25NGUK Division of Radiotherapy and imaging The Institute of Cancer ResearchLondon SM25NGUK

Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic *** role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being *** antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen *** lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting *** review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.

关键词： Antigen heterogeneity chimeric antigen receptor(CAR)T cells mesothelioma tumor-associated antigens(TAAs) bystander effect epitope spreading tumor microenvironment

Perfusion magnetic resonance imaging of the liver

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World Journal of Gastroenterology 2010年第13期16卷 1598-1609页

作者： Choon Hua Thng Tong San Koh David J Collins Dow Mu Koh Department of Oncologic imaging National Cancer Centre Department of Radiology Royal Marsden NHS Foundation Trust CR uk-EPSRC cancer imaging centre Institute of Cancer Research

Perfusion magnetic resonance imaging (MRI) studies quantify the microcirculatory status of liver parenchyma and liver lesions, and can be used for the detection of liver metastases, assessing the effectiveness of antiangiogenic therapy, evaluating tumor viability after anticancer therapy or ablation, and diagnosis of liver cirrhosis and its severity. In this review, we discuss the basic concepts of perfusion MRI using tracer kinetic modeling, the common kinetic models applied for analyses, the MR scanning techniques, methods of data processing, and evidence that supports its use from published clinical and research studies. Technical standardization and further studies will help to establish and validate perfusion MRI as a clinical imaging modality.

关键词： Magnetic resonance imaging Dynamic contrast-enhanced magnetic resonance imaging Liver Tracer kinetic modeling

SERIneALanine Killer:SPT promiscuity inhibits tumour growth via intra-tumoral deoxysphingolipid production

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Signal Transduction and Targeted Therapy 2020年第1期5卷 219-220页

作者： Mattia Falcone Oliver D.K.Maddocks University of Glasgow Institute of cancer Sciences Wolfson Wohl Cancer Research CentreGarscube EstateGlasgow G611QHUK

In a recent article in Nature,Muthusami et al.1 highlight the promiscuity of serine palmitoyltransferase(SPT)for non-essential amino acids under low serine conditions,illustrating a previously unappreciated mechanism ... 详细信息

关键词： Killer SPT tumour

A four-fold interpenetrated MOF for efficient perrhenate/pertechnetate removal from alkaline nuclear effluents

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Chinese Chemical Letters 2024年第12期35卷 550-554页

作者： Lei Zhu Hai-Ruo Li Yi-Ning Mao Ruiying Liu Bo Zhang Jing Chen Wengui Xu Libo Zhang Cheng-Peng Li Department of Molecular imaging and Nuclear Medicine Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Centre for CancerTianjin's Clinical Research Centre for CancerKey Laboratory of Cancer Prevention and Therapy Tianjin Key Laboratory of Structure and Performance for Functional Molecules College of ChemistryTianjin Normal University Department of Breast Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer Hospital&Chinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University

The sequestration of99Tc represents one of the most challenging tasks in nuclear waste decontamination In the event of a radioactive waste leak,99TcO4–(a main form of99Tc) would spread into the groundwa ter,a scenario difficult to address with conventional anion exchange materials like resin and inorganic cationic ***,we present a nickel（II） metal-organic framework （MOF）,TNU-143,featuring3D four-fold interpenetrated ***-143 exhibits efficient ReO4–(a nonradioactive analogue o99TcO4–) removal with fast anion exchange kinetics （<1 min）,high sorption capacity （844 mg/g for ReO4–）and outstanding selectivity over common *** importantly,TNU-143 shows superior stability in alkaline solution and can remove 91.6% ReO4–from simulated alkaline high-level waste （HLW） stream with solid-liquid ratio of 40 g/*** uptake mechanism is elucidated by the single-crystal structure o TNU-143（Re）,showing that ReO4–anions are firmly coordinated to nickel cation to result in a 2D lay ered *** functional theory （DFT） calculations confirm the transformation from TNU-143 to TNU-143（Re） is a thermodynamically favorable *** work presents a new approach to the removal of Re O4–/99TcO4–from alkaline nulcear fuel using MOF sorbents.

关键词： Metal-organic framework Perrhenate/pertechnetate adsorption Single crystal to single crystal transformation Alkaline nuclear effluents

Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1318-1331页

作者： Pedro Casado Ana Rio-Machin Juho JMiettinen Findlay Bewicke-Copley Kevin Rouault-Pierre Szilvia Krizsan Alun Parsons Vinothini Rajeeve Farideh Miraki-Moud David CTaussig Csaba Bödör John Gribben Caroline Heckman Jude Fitzgibbon Pedro R.Cutillas Cell Signalling and Proteomics Group Centre for Genomics and Computational BiologyBarts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK centre for Genomics and Computational Biology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Institute for Molecular Medicine Finland-FIMM HiLIFE-Helsinki Institute of Life ScienceiCAN Digital Precision Cancer Medicine FlagshipUniversity of HelsinkiHelsinkiFinland centre for Haemato-Oncology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK HCEMM-SU Molecular Oncohematology research Group 1st Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestBudapestHungary cancer research uk cancer Therapeutics Unit Division of Cancer TherapeuticsThe Institute of Cancer ResearchSuttonUK a The Alan Turing Institute The British Library2QR96 Euston RdLondon NW12DBUK

Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in uk and Finland)at the proteomic,phosphoproteomic and drug response phenotypic *** data were complemented with transcriptomics analysis for 39 *** integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and *** presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged *** was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other ***-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to *** expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to *** summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged *** data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.

关键词： metabolism signature biologically

Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed WMatthijs Blankesteijn Sébastien Foulquier Department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-School for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK centre for Trauma Sciences research University of BirminghamEdgbastonBirminghamUK MHeNs-School for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

Targeting cellular pathways in glioblastoma multiforme

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Signal Transduction and Targeted Therapy 2017年第1期2卷 89-99页

作者： Joshua RD Pearson Tarik Regad The John van Geest cancer research centre School of Science and TechnologyNottingham Trent UniversityClifton LaneNottinghamUK

Glioblastoma multiforme(GBM)is a debilitating disease that is associated with poor prognosis,short median patient survival and a very limited response to *** has a very complex pathogenesis that involves mutations and alterations of several key cellular pathways that are involved in cell proliferation,survival,migration and ***,efforts that are directed toward better understanding of GBM pathogenesis are essential to the development of efficient therapies that provide hope and extent patient *** this review,we outline the alterations commonly associated with GBM pathogenesis and summarize therapeutic strategies that are aimed at targeting aberrant cellular pathways in GBM.

关键词： alterations pathogenesis prognosis

Erratum to Genetic and molecular changes in ovarian cancer

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cancer Biology & Medicine 2017年第2期14卷 196-201页

作者： Robert L Hollis Charlie Gourley Edinburgh cancer research uk centre MRC Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH4 2XR UK

In the published article~, some errors appeared on page 238, Figure 1, and reference list. The editors and the authors apologize for the errors and for any confusion they may have caused. On page238, the sentence of ＂affecting 20% and 17.5% of cases＂ should be changed to ＂and that inactivation of these genes occurs in 17.5% and 20% of cases＂.

关键词：卵巢癌分子遗传勘误基因失活