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Identification of potential immune-related mechanisms related to the development of multiple myeloma

Chinese Medical Journal 2024年第13期137卷 1603-1613页

作者： Yaomei Wang Wenli Zhang Tiandong Li Mengmeng Liu Mengya Gao Xinqing Li Yufei Chen Yongping Song Wei Li Chunyan Du Fang Wang Lina Liu Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China The Academy of Medical Science College of MedicalZhengzhou UniversityZhengzhouHenan 450052China College of Public Health Zhengzhou UniversityZhengzhouHenan 450000China Department of Research and Foreign Affairs The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Department of Clinical Medicine Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Laboratory Animal Center School of Medical SciencesZhengzhou UniversityZhengzhouHenan 450052China

Background:Although significant advances have been made in the treatment of multiple myeloma(MM),leading to unprecedented response and survival rates among patients,the majority eventually relapse,and a cure remains *** situation is closely related to an incomplete understanding of the immune microenvironment,especially monocytes/macrophages in patients with treatment-naïve *** aim of this study was to provide insight into the immune microenvironment,especially monocytes/macrophages,in patients with treatment-naïve ***:This study used the single-cell RNA sequencing(scRNA-seq)data of both patients with MM and heathy donors to identify immune cells,including natural killer(NK)cells,T cells,dendritic cells(DCs),and monocytes/*** data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM ***:A significant difference was observed between the bone marrow(BM)immune cells of the healthy controls and treatment-naïve MM patients through *** is noteworthy that,through an scRNA-seq data analysis,this study found that interferon(IFN)-induced NK/T cells,terminally differentiated effector memory(TEMRA)cells,T-helper cells characterized by expression of IFN-stimulated genes(ISG^(+)Th cells),IFN-responding exhausted T cells,mannose receptor C-type 1(mrc1)^(+)DCs,IFN-responding DCs,MHCII^(+)DCs,and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve ***,transcriptomic data of monocytes/macrophages demonstrated that"don’t eat me"-related genes and IFN-induced genes increase in treatment-naïve MM ***,scRNA-seq,transcriptomic data,and flow cytometry also showed an increased proportion of CD16^(+)monocytes/macrophages and expression level of ***-cell communication analysis indicated that monocytes/macrophages,whose related important signaling pathways include migration i

关键词： Multiple myeloma Monocytes/macrophages Single-cell RNA sequencing Immune cell Microenvironment Bone marrow Molecular characterization

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Biomarkers in Barrett's esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

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World Journal of Gastroenterology 2010年第45期16卷 5669-5681页

作者： Chin-Ann J Ong Pierre Lao-Sirieix Rebecca C Fitzgerald mrc cancer Cell unit Hutchison-MRC Research CentreCambridgeCB20XZUnited Kingdom

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.

关键词： Barrett’s esophagus Esophageal adenocar cinoma Esophageal dysplasia Prognosis

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Breath Biopsy^(®) to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 638-648页

作者： Giuseppe Ferrandino Giovanna De Palo Antonio Murgia Owen Birch Ahmed Tawfike Rob Smith Irene Debiram-Beecham Olga Gandelman Graham Kibble Anne Marie Lydon Alice Groves Agnieszka Smolinska Max Allsworth Billy Boyle Marc P.van der Schee Michael Allison Rebecca C.Fitzgerald Matthew Hoare Victoria K.Snowdon Owlstone Medical CambridgeUK Department of Oncology University of CambridgeHutchison/MRC Research CentreCambridgeUK Department of Pharmacology and Toxicology School for Nutrition and Translational Research in Metabo-lism(NUTRIM)Maastricht University Medical Centerthe Netherlands Department of Medicine University of CambridgeAddenbrooke’s HospitalCambridgeUK Addenbrookes Hepatology and Liver Transplantation unit Addenbrookes Hospi-talCambridgeUK mrc cancer unit Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUK CRUK Cambridge Institute CambridgeUK

Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare *** is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease *** previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical ***:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from *** and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)***:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test *** seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component ***:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.

关键词： Breath Biopsy Non-invasive Biomarker Cirrhosis Liver function test.

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Genetic and molecular changes in ovarian cancer

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cancer Biology & Medicine 2016年第2期13卷 236-247页

作者： Robert L Hollis Charlie Gourley Edinburgh cancer Research UK Centre MRC Institute of Genetics and Molecular Medicine University of Edinburgh

Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical ***, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

关键词：分子水平遗传异质性卵巢癌基础生物学临床意义浆液性恶性肿瘤发达国家

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Human epidermal growth factor receptor targeted inhibitors for the treatment of ovarian cancer

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cancer Biology & Medicine 2018年第4期15卷 375-388页

作者： Maria Bonello ANDrew Harvey Sims Simon Peter Langdon cancer Research UK Edinburgh Center and Division of Pathology Laboratory MRC Institute of Genetics and Molecular Medicine University of Edinburgh

Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients,especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors. They have demonstrated valuable antitumor activity in multiple cancers and their possible use in ovarian cancer continues to be studied. In this review, we discuss the human epidermal growth factor receptor family; review emerging clinical studies on monoclonal antibodies and tyrosine kinase inhibitors targeting these receptors in ovarian cancer patients; and propose future research possibilities in this area.

关键词： Tyrosine kinase monoclonal antibodies ovarian cancer inhibitors HER receptors

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Human cancergermlineantigen-specific cytotoxicTcell-what canwelearnfrompatient

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Cellular & Molecular Immunology 2020年第7期17卷 684-692页

作者： Megat Abd Hamid Yanchun Peng Tao Dong Nufield Department of Medicine Chinese Academy of Medical Science Oxford Institute(COI)University of OxfordOxfordUK mrc Human Immunology unit MRC Weatherall Institute of Molecular MedicineUniversity of OxfordOxfordUK

In this review,we will highlight the importance of cancer germline antigen-specific cytotoxic CD8^(+) T lymphocytes(CTL)and the factors affecting antitumor CTL *** light of cancer immunotherapy,we will emphasis the need to further understand the features,characteristics,and actions of modulatory receptors of human cancer germline-specific CTLs,in order to determine the optimal conditions for antitumor CTL responses.

关键词： cytotoxic T cell immune check point receptor immune therapy T cell receptor cancer antigen

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mTOR-S6K1 pathway mediates cytoophidium assembly

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Journal of Genetics and Genomics 2019年第2期46卷 65-74页

作者： Zhe Sun Ji-Long Liu School of Life Science and Technology ShanghaiTech University mrc Functional Genomics unit Department of Physiology Anatomy and Genetics University of Oxford

CTP synthase(CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has been demonstrated to assemble into evolutionarily conserved filamentous structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian cells. However, the regulation and function of the cytoophidium remain elusive. Here, we provide evidence that the mechanistic target of rapamycin(mTOR) pathway controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 1(mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6 K1 can inhibit cytoophidium formation, while overexpression of the constitutively active S6 K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, reducing m TOR protein expression results in a decrease of the length of cytoophidium in Drosophila follicle ***, our study connects CTPS cytoophidium formation with the mTOR signaling pathway.

关键词： mTOR Cytoophidium CTP synthase Colorectal cancer cell Drosophila

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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

[This corrects the article on p. 236 in vol. 13, PMID: 27458531.].

关键词：卵巢癌分子遗传勘误基因失活

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The cellular metabolic landscape in the tumor milieu regulates the activity of myeloid infiltrates

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Cellular & Molecular Immunology 2018年第5期15卷 421-427页

作者： Eslam Mohamed Amir A.Al-Khami Paulo C.Rodriguez lee moffitt cancer center and research institute 12902 magnolia dr.mrc-annex 2ndtampafl 33612usa stanley s.scott cancer center louisiana state university health sciences centernew orleansla 70112usa

Malignant cells upregulate distinct energy metabolism programs that support their proliferation,migration,and adaptation to the stressful tumor microenvironment(TME).Additionally,this exaggerated metabolic activity allows cancer cells to hijack essential nutrients and outcompete neighboring infiltrating immune cells,thereby impairing antitumor *** recent years,there has been great interest in the field to understand the tumor-induced energy metabolism signals that regulate the function of immune cells in individuals with ***,it is now well accepted that uncovering the mechanisms that instruct the metabolic behavior of cancer cells and tumor-associated immune cells is an indispensable strategy for the development of new approaches to overcome immune suppression in ***,in this minireview,we briefly discuss the interaction between particular metabolic signaling pathways and immunosuppressive activity in different subsets of myeloid cells within the ***,we illustrate potential central mechanisms controlling the metabolic reprogramming of myeloid cells in response to tumor-derived factors.

关键词： Tumor microenvironment metabolic reprogramming immune suppression myeloid cells

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Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

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四川生理科学杂志 2024年第7期46卷 1635-1635页

作者： Anissa A Widjaja Cardiovascular and Metabolic Disorders Program Duke–National University of Singapore Medical School Singapore Singapore National Heart Research Institute Singapore National Heart Centre Singapore Singapore Singapore Institute for Big Data and Artificial Intelligence in Medicine School of Science China Pharmaceutical University Nanjing China mrc Laboratory of Medical Sciences London UK Barts Heart Centre Barts Health NHS Trust London UK Cardiovascular and Metabolic Sciences Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany DZHK (German Centre for Cardiovascular Research) Partner Site Berlin Berlin Germany Charité–Universitätsmedizin Berlin Germany Institute of Clinical Sciences Faculty of Medicine Imperial College London UK Bone Biology and Disease unit St Vincent’s Institute of Medical Research Melbourne Victoria Australia Department of Medicine St Vincent’s Hospital The University of Melbourne Melbourne Victoria Australia

For healthspan and lifespan,ERK,AMPK and mTORC1 represent critical pathways and inflammation is a centrally important *** we examined whether IL-11,a pro-inflammatory cytokine of the IL-6 family,has a negative effect on age-associated disease and *** mice age,IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular,tissue-and organismal-level ageing *** of Il11 or Il11ra1 protects against metabolic decline,multi-morbidity and frailty in old age.

关键词： inflammation mTORC1 life

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