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CD8+ cytotoxic T lymphocytes in human influenza virus infection

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National Science Review 2015年第3期2卷 264-265页

作者： Tao Dong mrc Human Immunology Unit Weatherall Institute of Molecular Medicine Oxford University CAMS-Oxford Joint Centre for Translational Immunology

Inluenza remains a global problem,resulting in 250 000–500 000 deaths in non-pandemic years according to the most recent WHO report(htp://***/mediacentre/factsheets/fs211/en/).he currently available inluenza vaccines mostly induce antibodies against the viral surface glycoproteins,haemagglutinin(HA)and neuraminidase,with the HA being by far the more *** neutralizing antibodies can provide sterilizing immunity by blocking infection,

关键词： cytotoxic T lymphocytes in human influenza virus infection In CD8 CTLs

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

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

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World Journal of Hepatology 2024年第3期16卷 366-378页

作者： Kanuengnit Choochuay Punna Kunhapan Apichaya Puangpetch Sissades Tongsima Pornpen Srisawasdi Abhasnee Sobhonslidsuk Somnuek Sungkanuparph Mohitosh Biswas Chonlaphat Sukasem Program in Translational medicine Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand School of Pharmacy Walailak UniversityNakhon Si Thammarat 80161Thailand Laboratory for Pharmacogenomics Division of Pharmacogenomics and Personalized MedicineSomdech Phra Debaratana Medical CenterDepartment of PathologyFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Department of Medical Sciences Ministry of Public HealthNonthaburi 11000Thailand National Biobank of Thailand National Center for Genetic Engineering and BiotechnologyPathum Thani 12120Thailand Division of Clinical Chemistry Department of PathologyFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Division of Gastroenterology and Hepatology Department of MedicineFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Chakri Naruebodindra Medical institute Faculty of Medicine Ramathibodi HospitalMahidol UniversitySamut Prakan 10540Thailand Department of Pharmacy University of RajshahiRajshahi 6205Bangladesh Pharmacogenomics Clinic Bumrungrad Genomic Medicine InstituteBumrungrad International HospitalBangkok 10110Thailand Research and Development Laboratory Bumrungrad International HospitalBangkok 10110Thailand mrc Centre for Drug Safety Science Department of Pharmacology and TherapeuticsInstitute of SystemsMolecular and Integrative BiologyUniversity of Liverpool Liverpool L693GLUnited Kingdom Faculty of Pharmaceutical Sciences Burapha UniversityChonburi 20131Thailand

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming *** To evaluate the associations of gene-polymorphism-related MAFLD in *** The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central *** single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related *** analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic *** The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus *** clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among *** The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

关键词： PNPLA3 LEP Metabolic-associated fatty liver disease People living with HIV Thai

Themis2:setting the threshold for B-cell selection

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Cellular & molecular Immunology 2017年第8期14卷 643-645页

作者： Mukta Deobagkar-Lele Consuelo Anzilotti Richard J Cornall mrc Human Immunology Unit Weatherall Institute for Molecular MedicineNuffield Department of MedicineUniversity of OxfordOxford OX3 9DSUK

The strength of signal downstream of the B-cell receptor(BCR)determines the positive and negative selection of B *** of a functional BCR is required for the selection of immature B cells into the peripheral repertoire in the absence of antigen;but selection is also modulated by avidity and affinity-dependent interactions with self and foreign antigens.

关键词： selection absence antigens

The Role of Chromatin Modifications in Progression through Mouse Meiotic Prophase

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Journal of Genetics and Genomics 2014年第3期41卷 97-106页

作者： James H.Crichton Christopher J.Playfoot Ian R.Adams mrc Human Genetics Unit MRC Institute of Genetics and Molecular MedicineUniversity of EdinburghWestern General Hospital

Meiosis is a key event in gametogenesis that generates new combinations of genetic information and is required to reduce the chro- mosome content of the gametes. Meiotic chromosomes undergo a number of specialised events during prophase to allow meiotic recombination, homologous chromosome synapsis and reductional chromosome segregation to occur. In mammalian cells, DNA phys- ically associates with histones to form chromatin, which can be modified by methylation, phosphorylation, ubiquitination and acetylation to help regulate higher order chromatin structure, gene expression, and chromosome organisation. Recent studies have identified some of the enzymes responsible for generating chromatin modifications in meiotic mammalian cells, and shown that these chromatin modifying enzymes are required for key meiosis-specific events that occur during meiotic prophase. This review will discuss the role of chromatin modifications in meiotic recombination, homologous chromosome synapsis and regulation of meiotic gene expression in mammals.

关键词： Mouse Meiosis Chromatin Chromosome Histone modification DNA methylation

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： ovarian cancer molecular genetics histological subtypes molecular subgrouping ovary

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

A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

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Journal of Genetics and Genomics 2024年第9期51卷 922-933页

作者： Ting Li Tursunjan Aziz Guangyuan Li Lin Zhang Jihua Yao Shunji Jia School of Life Sciences Fudan UniversityShanghai 200438China State Key Laboratory of Membrane Biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular *** in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(mrc)*** development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical *** this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid *** this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing *** data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

关键词： Tufm Mitochondria COXPD4 Disease model Zebrafish

Why some tumours trigger neovascularisation and others don't:the story thus far

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Chinese Journal of Cancer 2016年第2期35卷 69-79页

作者： Omanma Adighibe Russell D.Leek Marta Fernandez-Mercado Jiangting Hu Cameron Snell Kevin C.Gatter Adrian L.Harris Francesco Pezzella Radcliffe Department of medicine Nuffield Division of Laboratory ScienceJohn Radcliffe HospitalUniversity of Oxford Radcliffe Department of medicine Leukaemia and Lymphoma Research Molecular Haematology UnitNuffield Division of Laboratory ScienceJohn Radcliffe Hospital Biodonostia Research institute Department of Medical Oncology Molecular Oncology LaboratoriesWeatherall Institute of Molecular MedicineJohn Radcliffe Hospital

Background:Angiogenesis is not essential for tumours to develop and expand,as cancer can also grow in a nonangiogenic fashion,but why this type of growth occurs is ***,our data from mRNA transcription profiling did not show any differences in the classical angiogenic pathways,but differences were observed in mitochondrial metabolic pathways,suggesting a key role for metabolic *** then validated these results with mRNA profiling by investigating differential protein expression via immunohistochemistry in angiogenic and non-angiogenic non-small cell lung cancers(NSCLCs).Methods:Immunohistochemical staining for 35 angiogenesis- and hypoxia-related biomarkers were performed on a collection of 194 angiogenic and 73 non-angiogenic NSCLCs arranged on tissue *** of P53 was performed with frozen tissue samples of ***:The non-angiogenic tumours were distinguished from the angiogenic ones by having higher levels of proteins associated with ephrin pathways,mitochondria,cell biogenesis,and hypoxia-inducible factor 1(HIF1) regulation by oxygen and transcription of HIF-controlled genes but lower levels of proteins involved in the stroma,cell-cell signaling and adhesion,integrins,and Delta-Notch and epidermal growth factor(EGF)-related ***,proteins classically associated with angiogenesis were present in both types of tumours at very comparable *** expression of P53 was strongly associated with non-angiogenic tumours.A pilot investigation showed that P53 mutations were observed in 32.0%of angiogenic cases but in 71.4%of non-angiogenic ***:Our observations thus far indicate that both angiogenic and non-angiogenic tumours experience hypoxia/HIF and vascular endothelial growth factor(VEGF) pathway protein expression in a comparable ***,angiogenesis does not ensue in the non-angiogenic ***,metabolic reprogramming seems to distinguish these two types of ne

关键词： Cancer, Angiogenesis, Hypoxia, Blood vessels