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Natural killer cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第24期27卷 3483-3501页

作者： Rachel Elizabeth Ann Fincham Francesca Romana Delvecchio Michelle R Goulart Joe Poe Sheng Yeong Hemant M Kocher Barts cancer Institute-CRUK Centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Institute of Molecular and Cellular Biology Agency for ScienceTechnology and ResearchSingapore 138673Singapore Centre for tumour Biology Barts Cancer Institute-CRUK Centre of ExcellenceQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic cancer remains one of medicine’s largest areas of unmet *** five-year survival rates of<8%,little improvement has been made in the last 50 *** presenting with advance stage disease,treatment options are **... 详细信息

Pancreatic cancer remains one of medicine’s largest areas of unmet *** five-year survival rates ofstromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer *** killer(NK)cells are crucial effector units in cancer *** used as a prognostic biomarker in a range of malignancies,NK cells have received much attention as an attractive target for immunotherapies,both as cell therapy and as a pharmaceutical *** this interest,the role of NK cells in pancreatic cancer remains poorly ***,increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to ***,we review the role of NK cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.

关键词： Pancreatic cancer Natural killer cells tumour microenvironment Pancreatic cancer stroma stromal cells

Antiangiogenic therapy:a novel approach to overcome tumor hypoxia

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Chinese Journal of cancer 2010年第8期29卷 715-720页

作者： Fang Peng1,2, Ming Chen1,2 1 State Key laboratory of Oncology in South China, Guangzhou, Guangdong 510060, P. R. China 2 Department of Radiation Oncology, Sun Yat-sen University cancer Center, Guangzhou, Guangdong 510060, P. R. China Department of Radiation Oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The growth and metastasis of solid tumors rely on blood vessels. Antiangiogenic agents mainly target tumor blood vessels, and radiation therapy mainly targets tumor cells. Combination of antiangiogenic treatment and radiation exhibits synergistic effect, which improves the response of tumors to radiation therapy. The mechanisms of interaction between antiangiogenic agents and ionizing radiation are complex and involve interactions between tumor cells and tumor microenvironment, including tumor oxygenation, stroma, and vasculature. The original mechanism of antiangiogenesis is to induce ischemia and hypoxia in tumors, thereby, "starve" the tumors. However, recently, emerging data suggest that antiangiogenic agents could reduce the proportion of hypoxic cells through normalizing tumor vasculature, decreasing oxygen consumption, and other mechanisms. The use of antiangiogenic agents provides a new approach to overcome the hypoxia problem, and ultimately improves the efficacy of radiation therapy. In this review, we discuss tumor hypoxia, tumor angiogenesis and its regulation, mechanisms of antiangiogenic therapy combined with radiation therapy, and how antiangiogenic therapy overcomes tumor hypoxia.

关键词：抗血管生成肿瘤细胞抗缺氧疗法放射治疗电离辐射肿瘤血管生成相互作用

Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

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Military Medical Research 2023年第3期10卷 383-402页

作者： Pei-Heng Li Xiang-Yu Kong Ya-Zhou He Yi Liu Xi Peng Zhi‑Hui Li Heng Xu Han Luo Jihwan Park Department of Thyroid and Parathyroid Surgery Laboratory of Thyroid and Parathyroid DiseaseFrontiers Science Centre for Disease‑Related Molecular NetworkDepartment of General SurgeryWest China HospitalSichuan UniversityChengdu 610044China Department of Oncology West China School of Public Health and West China Fourth HospitalSichuan UniversityChengdu 610044China Department of Rheumatology and Immunology Rare Diseases CentreWest China HospitalSichuan UniversityChengdu 610044China College of Computer Science Sichuan UniversityChengdu 610065China State Key laboratory of Biotherapy and cancer Centre West China HospitalSichuan University and Collaborative Innovation CentreChengdu 610044China School of Life Sciences Gwangju Instituteof Science and Technology(GIST)Gwangju 61005Republic of Korea

The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the *** time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high *** this review,we first introduced the principle of scRNA-seq and compared different sequencing *** cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in ***,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in *** also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the *** addition,the therapeutic interventions based on cellular interactions in TIME were also *** decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of *** the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the ***,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

关键词： Single-cell RNA sequencing(scRNA-seq) tumour immune microenvironment(TIME) Trajectory Cellular interactions Therapeutic targets

程序性细胞死亡配体1在结直肠癌肝脏寡转移灶的表达及其预后价值

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Gastroenterology Report 2021年第5期9卷 443-450,I0002页

作者： Jian-Hong Peng Yi Tai Yi-Xin Zhao Bao-Jia Luo Qing-Jian Ou Zhi-Zhong Pan Lin Zhang Zhen-Hai Lu Department of Colorectal Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine GuangzhouGuangdongP.R.China Department of Clinical laboratory Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China

背景:程序性细胞死亡配体1(PD-L1)在结直肠癌肝脏寡转移灶(CLO)表达的临床价值尚不明确。本研究旨在检测CLO微环境中PDL1的表达,并分析其与患者预后的关系。方法:收集1999年6月至2016年12月之间126例行根治性肝切除术的CLO患者的肝转移... 详细信息

背景:程序性细胞死亡配体1(PD-L1)在结直肠癌肝脏寡转移灶(CLO)表达的临床价值尚不明确。本研究旨在检测CLO微环境中PDL1的表达,并分析其与患者预后的关系。方法:收集1999年6月至2016年12月之间126例行根治性肝切除术的CLO患者的肝转移瘤标本。免疫组织化学法检测PD-L1在石蜡包埋标本中的表达水平。采用Kaplan-Meier法和Log-rank检验分析总体生存(OS)和无复发生存(RFS)。结果:PD-L1主要在肝转移灶的间质中表达。PD-L1高表达患者的临床风险更高(临床风险评分2–4分者比例:67.7%vs 40.4%,P=0.004)。中位随访58个月,PD-L1高表达患者3年OS(65.5%vs 92.7%,P=0.001)和3年RFS(34.7%vs 83.8%,P<0.001)均显著低于PD-L1低表达者。多因素Cox分析显示,PD-L1高表达(HR=3.581;95%CI 2.301–9.972,P=0.015),CRS 2–4分(HR=6.960,95%CI 1.135–42.689,P=0.036)及术前CA19-9增高(HR=2.843,95%CI 1.229–6.576,P=0.015)是OS的独立危险因素。PD-L1高表达(HR=4.815,95%CI 2.139–10.837,P<0.001)和原发灶淋巴结转移(HR=2.115,95%CI 1.041–4.297,P=0.038)是RFS的独立危险因素。结论:本研究发现PD-L1在CLO患者的肝转移灶间质中普遍表达,其高表达提示预后不良。

关键词： PD-L1 colorectal liver oligometastases expression prognosis

Weighted gene co-expression network analysis identiffes potential regulators in response to Salmonella Enteritidis challenge in the reproductive tract of laying ducks

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Journal of Integrative Agriculture 2022年第8期21卷 2384-2398页

作者： ZHANG Yu LUO Shu-wen HOU Li-e GU Tian-tian ZHU Guo-qiang Wanwipa VONGSANGNAK XU Qi CHEN Guo-hong Joint International Research laboratory of Agriculture and Agri-Product Safety of Ministry of Education Yangzhou UniversityYangzhou 225009P.R.China Jiangsu Key laboratory of Zoonosis Yangzhou UniversityYangzhou 225009P.R.China Department of Zoology Faculty of ScienceKasetsart UniversityBangkok 10900Thailand

Salmonella Enteritidis(SE)is a zoonotic and vertically transmitted pathogen,often colonized in the reproductive tract of adult poultry,which can result in direct contamination of eggs and threaten human *** studies have revealed that some pattern recognition receptors and resistance genes were involved in regulating immune responses to SE invasion in ***,the role of these immune response genes was not independent,and the interactions among the genes remained to be further *** this study,SE burden and colonization were determined in reproductive tissue after the ducks were SE-infected,and RNA-sequencing was performed to construct co-expression networks by weighted gene co-expression network analysis(WGCNA).The result showed that SE could be isolated from 22% of infected-birds in any segment of the reproductive tract and the SE was readily colonized in the stroma,small follicle,isthmus,and vagina of the reproductive tracts in morbid *** top central,highly connected genes were subsequently identified three specific modules in the above four tissues at the defined cut-offs(P<0.01),including 60 new candidate regulators and 125 transcription ***,those 185 differentially expressed genes(DEGs)in these modules were ***,the hub genes(TRAF3,CXCR4 and IL13RA1)were identified to act with many other genes through immune response pathways including NF-kappaB,Toll-like receptor,steroid biosynthesis,and p53signaling *** data provide references that will understand the immune regulatory relationships during SE infection,but also assist in the breeding of SE-resistant lines through potential biomarkers.

关键词： duck Salmonella Enteritidis reproductive tract infection-related genes WGCNA

T cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第46期27卷 7956-7968页

作者： Michelle R Goulart Konstantinos Stasinos Rachel Elizabeth Ann Fincham Francesca R Delvecchio Hemant M Kocher Centre for tumour Biology Barts cancer Institute-A CRUK Centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre The Royal London HospitalBarts Health NHS TrustLondon E11BBUnited Kingdom Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival *** has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T *** cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant *** tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted ***,we review the role of T cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.

关键词： Immunosuppression T cell exhaustion tumour microenvironment Pancreatic ductal adenocarcinoma Pancreatic cancer stroma

SILAC–based quantitative MS analysis for protein-mediated cell-cell interactions

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SILAC–based quantitative MS analysis for protein-mediated c...

Differential role of Hedgehog signaling in human pancreatic(patho-)physiology:An up to date review

中国生物化学与分子生物学会2016年全国学术会议

作者： Xixi Wang Pengbo Yang Shufang Liang State Key laboratory of Biotherapy and cancer Center West China HospitalSichuan University / National

In tumor microenvironment, interactions among multiple cell types are critical for cancer progression. To understand the molecular mechanisms of these complex interplays, the secreted protein analysis between malignant cancer cells and the surrounding nonmalignant stroma is a good viewpoint to investigate cell-cell interactions. Here, we develop two methods termed ‘spike-in SILAC’ and ‘triple-SILAC’ to quantify the changes of secretome in a co-cultured system of CT26 and Ana-1 cells(Figure 1). As results, compared with mono-cultured cells, 188 and 56 secreted proteins were identified to change in the co-cultured system by ‘spike-in SILAC’ and ‘triple-SILAC’ methods respectively. The Figure 2 was shown three representative both-identified proteins(Galectin-1, Cathepsin L1 and Thrombospondin-1) by SILAC-based mass spectra(MS), in which pairs of isotope labeling peaks reflected the expression change of a protein in the co-cultured cell system. To validate the accuracy of MS analysis, cell supernatant was collected to detect the secretion level of the three proteins by Western blotting, and the results matched very well(Figure 3). So far the ‘spike-in SILAC’ and ‘triple-SILAC’ based quantitative MS approaches are sensitive to measure protein secretion changes due to cell-cell interactions of two different types of cells in vitro.

关键词： Secretome Co-culture Quantitative proteomics Spike-in SILAC triple-SILAC tumor microenvironment

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World Journal of Gastrointestinal Pathophysiology 2016年第2期7卷 199-210页

作者： Eckhard Klieser Stefan Swierczynski Christian Mayr Tarkan Jager Johanna Schmidt Daniel Neureiter Tobias Kiesslich Romana Illig Institute of Pathology Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Surgery Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Internal Medicine I Paracelsus Medical UniversitySalzburger Landeskliniken(SALK) laboratory for tumour Biology and Experimental Therapies(TREAT) Institute of Physiology and PathophysiologyParacelsus Medical University

Since the discovery of the Hedgehog(Hh)pathway in drosophila melanogaster,our knowledge of the role of Hh in embryonic development,inflammation,and cancerogenesis in humans has dramatically increased over the last *** is the case especially concerning the pancreas,however,real therapeutic breakthroughs are missing until *** general,Hh signaling is essential for pancreatic organogenesis,development,and tissue *** the case of acute pancreatitis,Hh has a protective role,whereas in chronic pancreatitis,Hh interacts with pancreatic stellate cells,leading to destructive parenchym fibrosis and atrophy,as well as to irregular tissue remodeling with potency of initiating *** vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor *** application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials(phases 1 and 2).Furthermore,a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic *** this review,we give a structured survey of the role of the Hh pathway in pancreatic development,pancreatitis,pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

关键词： Pancreatic cancer Hedgehog Pancreatitis Pancreas Development

Nat Cell Biol:研究发现乳腺癌的新型细胞起源

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现代生物医学进展 2017年第8期17卷 I0002-I0002页

作者： Leander Blaas, Agneta B. Andersson, Marco Gerling, Alexandra Musch, Dorothee Bornhorst Rune Toftg #x000E5 rd Fabio Pucci, Hendrik A. Messal, E. Josue Ruiz Axel Behrens Iyadh Douagi Bradley Spencer-Dene, Richard Stone Gordon Stamp Richard Mitter Leena Bhaw Abdul K. Sesay Jos Jonkers Ilaria Malanchi Axel Behrens Center for Innovative Medicine (CIMED) Department of Biosciences and Nutrition Karolinska Institutet Novum 141 83 Huddinge Sweden Adult Stem Cell laboratory The Francis Crick Institute 1 Midland Road London NW1 1AT UK Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Novum 141 83 Huddinge Sweden Experimental Histopathology The Francis Crick Institute 1 Midland Road London NW1 1AT UK Bioinformatics and Biostatistics The Francis Crick Institute 1 Midland Road London NW1 1AT UK Advanced Sequencing Facility The Francis Crick Institute Mill Hill Laboratory The Ridgeway London NW7 1AA UK Division of Molecular Pathology and cancer The Netherlands Cancer Institute 1066 CX Amsterdam The Netherlands tumour-stroma interactions in cancer laboratory The Francis Crick Institute 1 Midland Road London NW1 1AT UK Faculty of Life Sciences & Medicine King&#x02019 s College London Guy&#x02019 s Campus London SE1 1UL UK

乳腺癌是女性常见的癌症类型之一，长期以来科学家们知道并不是所有的乳腺癌都是相似的，腔体肿瘤主要包含一些和乳腺管内层细胞非常相似的细胞类型，而其它肿瘤所包含的细胞则同乳腺上皮组织外层的细胞相似，研究者认为，这种多样性起... 详细信息

乳腺癌是女性常见的癌症类型之一，长期以来科学家们知道并不是所有的乳腺癌都是相似的，腔体肿瘤主要包含一些和乳腺管内层细胞非常相似的细胞类型，而其它肿瘤所包含的细胞则同乳腺上皮组织外层的细胞相似，研究者认为，这种多样性起源于不同干细胞或祖细胞的突变，

关键词：细胞起源乳腺癌 Cell Nat 细胞类型上皮组织种多样性相似