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Forensic Sciences Research 2019年第3期4卷 247-256页

作者： Thomas Hadberg Lynge Trine Skov Nielsen Bo Gregers Winkel Jacob Tfelt-Hansen Jytte Banner Department of Cardiology RigshospitaletDenmarkSection of Forensic PathologyAarhus UniversityAarhusDenmark Department of Forensic Medicine Section of Forensic PathologyAarhus UniversityAarhusDenmark Department of Forensic Medicine Section of Forensic PathologyCopenhagen UniversityCopenhagenDenmark

Myocarditis is associated with an increased risk of sudden cardiac death (SCD) in the ***,Information on nationwide burden of SCD caused by myocarditis (SCD-myocarditis) is *** this study all deaths among persons in Denmark aged 1-35years in 2000-2009 and 36-49years in 2007-2009 (27.1 million person-years) were *** reports,death certificates,discharge summaries,and nationwide registries were used to identify all cases of *** the 10-year study period,there were 14294 deaths,of which we identified 1 363 (10%) *** autopsied SCD (n=753,55%),cause of death was myocarditis in 42 (6%) cases corresponding to an SCD-myocarditis incidence of 0.16 (95%CI: 0.11-0.21) per 100000 *** had significantly higher incidence rates of SCD-myocarditis compared to females with an incidence rate ratio of 2.2 (95%CI:1.1-4.1).Myocarditis was not registered as cause of death In any of the non-autopsied SCD (n=610,45%).In conclusion,after nationwide unselected Inclusion of 14294 deaths,we found that 6% of all autopsied SCD was caused by *** cases of SCD-myocarditis were reported in the non-autopsied SCD,which could reflect underdiagnosing of myocarditis in non-autopsied ***,our data suggest a female protection towards SCDmyocarditis.

关键词： Forensic sciences sudden cardiac death myocarditis autopsy epidemiology gender children young adults

Cancer risk and mortality in patients with solitary Peutz–Jeghers polyps

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Gastroenterology Report 2023年第1期11卷 576-578页

作者： Anne Marie Jelsig Laus Wullum Lilian Bomme Ousager Johan Burish Tine Plato Kuhlmann John Gasdal Karstensen Department of Clinical Genetics University Hospital of CopenhagenRigshospitaletCopenhagenDenmark Omicron Aps CopenhagenDenmark Department of Clinical Genetics Odense University HospitalOdenseDenmark Human Genetics Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark Gastrounit Medical DivisionCopenhagen University Hospital—Amager and HvidovreHvidovreDenmark Department of Pathology Copenhagen University HospitalHerlevDenmark Department of Clinical Medicine University of CopenhagenCopenhagenDenmark Danish Polyposis Registry GastrounitCopenhagen University Hospital—Amager and HvidovreHvidovreDenmark

Introduction Solitary Peutz–Jeghers polyps are hamartomatous lesions in the gastrointestinal(GI)*** are rare and can be diagnosed in both children and adults(Figure 1A).Microscopically,Peutz–Jeghers polyps can have ... 详细信息

关键词： Jeghers Peutz polyps

Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner

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Cellular & Molecular Immunology 2021年第2期18卷 415-426页

作者： Morten Orebo Holmström Rasmus Erik Johansson Mortensen Angelos Michail Pavlidis Evelina Martinenaite Stine Emilie Weis-Banke Mia Aaboe-Jørgensen Simone Kloch Bendtsen Özcan Met Ayako Wakatsuki Pedersen Marco Donia Inge Marie Svane Mads Hald Andersen Department of Oncology National Center for Cancer Immune TherapyCopenhagen University HospitalHerlevDenmark IO Biotech ApS CopenhagenDenmark Institute for Immunology and Microbiology Copenhagen UniversityCopenhagenDenmark

Transforming growth factor-beta(TGFβ)is a highly potent immunosuppressive *** TGFβis a tumor suppressor in early/premalignant cancer lesions,the cytokine has several tumor-promoting effects in advanced cancer;abrogation of the antitumor immune response is one of the most important tumor-promoting *** several immunoregulatory mechanisms have recently been shown to be targets of specific T cells,we hypothesized that TGFβis targeted by naturally occurring specific T cells and thus could be a potential target for immunomodulatory cancer ***,we tested healthy donor and cancer patient T cells for spontaneous T-cell responses specifically targeting 3820-mer epitopes derived from TGFβ*** identified numerous CD4^(+)and CD8^(+)T-cell responses against several epitopes in TGFβ.Additionally,several ex vivo responses were *** enriching specific T cells from different donors,we produced highly specific cultures specific to several TGFβ-derived *** CD8^(+)T-cell clones specific for both a 20-mer epitope and a 9-mer HLA-A2 restricted killed epitope peptide were pulsed in HLA-A2+target cells and killed the HLA-A2+cancer cell lines THP-1 and ***,stimulation of THP-1 cancer cells with cytokines that increased TGFβexpression increased the fraction of killed *** conclusion,we have shown that healthy donors and cancer patients harbor CD4^(+)and CD8^(+)T cells specific for TGFβ-derived epitopes and that cytotoxic T cells with specificity toward TGFβ-derived epitopes are able to recognize and kill cancer cell lines in a TGFβ-dependent manner.

关键词： Immune regulation TGFbeta cancer T cells adaptive immunity

Characterization of TGFβ-specific CD4+T cells through the modulation of TGFβexpression in malignant myeloid cells

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Cellular & Molecular Immunology 2021年第11期18卷 2575-2577页

作者： Rasmus Erik Johansson Mortensen Morten Orebo Holmström Mads Hald Andersen National Center for Cancer Immune Therapy Department of OncologyCopenhagen University HospitalHerlevDenmark Institute for Immunology and Microbiology Copenhagen UniversityCopenhagenDenmark

Transforming growth factor beta(TGFβ)is a pleiotropic cytokine with functions related to angiogenesis,tumor suppression,and immune tolerance[1].TGFβis involved in tumor immune escape and is a target for cancer immune therapy[1].We have reported that healthy donors and cancer patients harbor CD8^(+)cytotoxic T lymphocytes(CTLs)that are specific to TGFβ-derived epitopes and that these CD8^(+)CTLs kill malignant myeloid cells in a TGFβ-dependent manner[2].

关键词： TGFβ malignant myeloid

人重组卵泡刺激素和表皮生长因子对性未成熟小鼠卵母细胞和颗粒细胞复合体体外发育的作用

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Developmental and Reproductive Biology 2001年第1期10卷 20-30页

作者：王海滨夏国良等中国农业大学生物学院中国北京100094

卵泡刺激素（FSH）对有腔卵泡和排卵前卵泡的促生命作用已被普遍接受，但关于其对腔前卵泡发育的作用报道结果不尽相同，关于表皮生长因子（EGF）对腔前卵泡的作用尚不确切，本研究目的在于探讨人重组卵泡刺激素（rechFSH)和EGF对早期... 详细信息

卵泡刺激素（FSH）对有腔卵泡和排卵前卵泡的促生命作用已被普遍接受，但关于其对腔前卵泡发育的作用报道结果不尽相同，关于表皮生长因子（EGF）对腔前卵泡的作用尚不确切，本研究目的在于探讨人重组卵泡刺激素（rechFSH)和EGF对早期卵泡发育的作用，利用胶原酶消化法从12日龄的小鼠卵巢中分离得到卵母细胞－颗粒细胞复合体（OGCs)(Fig.1)。体外每孔30－40个培养物并分别添加胎牛血清（FBS），rechFSH和EGF。培养物每4天测量卵母细胞和OGCs直径，并每天照相，结果显示，rechFSH显著促进小鼠OGCs 及其卵母细胞的体外发育，这一作用可被EGF进一步增强（P＜0．05）（Fig.2),但到第八天培养结束时，培养后的OGCs卵母细胞要显著小于体内期生长对照组（P＜0．05）（Fig.3)，说明FSH和EGF在卵泡早期发育中起重要作用。

关键词：人重组卵泡刺激性表皮生长因子性未成熟卵母细胞颗粒细胞复合体体外发育

C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

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World Journal of Clinical Oncology 2014年第4期5卷 621-632页

作者： Benedikte Jacobsen Mette Camilla Kriegbaum Eric Santoni-Rugiu Michael Ploug The Finsen Laboratory Rigshospitalet Copenhagen Biocenter 2200 Copenhagen Denmark Biotech Research and Innovation Centre University of Copenhagen 2200 Copenhagen Denmark Department of Pathology Diagnostic Center Rigshospitalet Copenhagen University Hospital 2100 Copenhagen Denmark 2^(nd) Danish-Chinese Centre for Proteases and Cancer

The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uP AR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasivecarcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.

关键词： LYPD3 Non-small cell lung cancer Prognosis Solid growth pattern Liver kinase B1 Precursor lesions Atypical adenomatous hyperplasia Metaplasia Squamous differentiation Ly6/Urokinase-type plasminogen activator receptor