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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 oftumour 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

Pancreatic cancer organotypics: High throughput, preclinical models for pharmacological agent evaluation

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World Journal of Gastroenterology 2014年第26期20卷 8471-8481页

作者： Stacey J Coleman Jennifer Watt Prabhu Arumugam Leonardo Solaini Elisabeta Carapuca Mohammed Ghallab Richard P Grose Hemant M Kocher centre for tumour biology Barts Cancer Institute - a CR-UK Centre of ExcellenceQueen Mary University of LondonJohn Vane Science CentreCharterhouse SquareLondon EC1M 6BQUnited Kingdom Barts and the London HPB centre The Royal London HospitalBarts Health NHS TrustLondon EC1M 6BQUnited Kingdom

Pancreatic cancer carries a terrible prognosis,as the fourth most common cause of cancer death in the Western *** is clearly a need for new therapies to treat this *** of the reasons no effective treatment has been developed in the past decade may in part,be explained by the diverse influences exerted by the tumour *** tumour stroma cross-talk in pancreatic cancer can influence chemotherapy delivery and response ***,appropriate preclinical in vitro models which can bridge simple 2D in vitro cell based assays and complex in vivo models are required to understand the biology of pancreatic *** we discuss the evolution of 3D organotypic models,which recapitulare the morphological and functional features of pancreatic ductal adenocarcinoma(PDAC).Organotypic cultures are a valid high throughput preclinical in vitro model that maybe a useful tool to help establish new therapies for PDAC.A huge advantage of the organotypic model system is that any component of the model can be easily modulated in a short *** allows new therapies that can target the cancer,the stromal compartment or both to be tested in a model that mirrors the in vivo situation.A major challenge for the future is to expand the cellular composition of the organotypic model to further develop a system that mimics the PDAC environment more *** discuss how this challenge is being met to increase our understanding of this terrible disease and develop novel therapies that can improve the prognosis for patients.

关键词： 3D organotypic model Pancreatic cancer Pancreatic stellate cell Stroma Preclinical models

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

Nutritional and vitamin status in patients with neuroendocrine neoplasms

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World Journal of Gastroenterology 2019年第10期25卷 1171-1184页

作者： Dominique SVM Clement Margot ET Tesselaar Monique E van Leerdam Rajaventhan Srirajaskanthan John K Ramage Neuroendocrine tumour Unit King’s College Hospital ENETS Centre of Excellence Department of Medical Oncology Netherlands Cancer Institute ENETS Centre of Excellence Department of Gastrointestinal Oncology Netherlands Cancer Institute Department of Gastroenterology King’s College Hospital

Symptoms of gastroenteropancreatic located neuroendocrine neoplasms(GEPNENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs.

关键词： Neuroendocrine neoplasm Nutrition Malnutrition Vitamin deficiency Diarrhoea Steatorrhoea

Molecular genetics of ependymoma

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Chinese Journal of Cancer 2011年第10期30卷 669-681页

作者： Yuan Yao Stephen C. Mack Michael D. Taylor Division of Neurosurgery Arthur and Sonia LabattBrain Tumour Research Centre Hospital for Sick Children TorontoOntario Canada Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada.

Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical *** mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained *** recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal *** heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this *** these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling *** characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of *** review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.

关键词：分子遗传学室管膜肿瘤发生发病机制手术切除动物模型遗传变异遗传特性

The role of MDM2 and MDM4 in breast cancer development and prevention

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Journal of Molecular Cell biology 2017年第1期9卷 53-61页

作者： Sue Haupt Reshma Vijayakumaran Panimaya Jeffreena Miranda Andrew Burgess Elgene Lim Ygal Haup tumour Suppression Laboratory Peter MacCallum Cancer Centre Melbourne 3000 Australia Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne 3000 Australia The Kinghorn Cancer centre Garvan Institute of Medical Research Sydney New South Wales 2010 Australia St. Vincent's Clinical School Faculty of Medicine University of New South Wales Sydney New South Wales 2010 Australia Department of Pathology The University of Melbourne Parkville Victoria 3010 Australia Department of Biochemistry and Molecular biology Monash University Clayton Australia

The major cause of death from breast cancer is not the primary turnout, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defence against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute （MDM） family： comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relerant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy ceils and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.

关键词： MDM2 MDM4 TP53 p53 breast cancer

Towards a multiscale model of colorectal cancer

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World Journal of Gastroenterology 2007年第9期13卷 1399-1407页

作者： Ingeborg MM van Leeuwen Carina M Edwards Mohammad Ilyas Helen M Byrne centre for Mathematical Medicine and biology School of Mathematical Sciences University of Nottingham Nottingham NG7 2RD United Kingdom centre for Mathematical biology Oxford Centre for Industrial and Applied Mathematics Mathematical Institute University of Oxford Oxford OX1 3LB United Kingdom Division of Pathology School of Molecular Medical SciencesQueen’s Medical Centre University of Nottingham Nottingham NG7 2UHUnited Kingdom

Colorectal cancer (CRC) is one of the best characterised cancers, with extensive data documenting the sequential gene mutations that underlie its development. Complementary datasets are also being generated describing changes in protein and RNA expression, tumour biology and clinical outcome. Both the quantity and the variety of information are inexorably increasing and there is now an accompanying need to integrate these highly disparate datasets. In this article we aim to explain why we believe that mathematical modelling represents a natural tool or language with which to integrate these data and, in so doing, to provide insight into CRC.

关键词： Intestinal epithelium Crypt fission APC mutations Mathematical modelling Stem cell niche Wnt signalling

Squamous cell carcinoma after radiofrequency ablation for Barrett's dysplasia

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World Journal of Gastroenterology 2014年第15期20卷 4453-4456页

作者： Sebastian S Zeki Rehan Haidry Manuel Justo-Rodriguez Laurence B Lovat Nicholas A Wright Stuart A McDonald centre for tumour biology Bart’s Cancer InstituteLondon EC1M 6BQUnited Kingdom Research Department of General Surgery University College LondonLondon WC1E 6BTUnited Kingdom Department of Pathology University College LondonLondon WC1E 6BTUnited Kingdom

Barrett’s oesophagus(BO)is a usually indolent condition that occasionally requires endoscopic *** ablation(RFA)is an effective endoscopic treatment for high grade dysplasia(HGD)and intramucosal cancer in *** has a good efficacy,durability and safety profile although complications can *** we describe a case of RFA in a patient with high grade *** the response to treatment was initially very good with the development of neosquamous epithelium,the patient very rapidly developed a squamous cell cancer of the oesophagus confirmed on radiology,histology and *** sequencing confirmed that the original HGD and the squamous cell cancer(SCC)were derived from separate clonal *** report highlights the fact that SCC of the oesophagus has been noted after endoscopic ablation for BO previously and suggest that ablation of BO may encourage the clonal expansion of cells carrying carcinogenic mutations once a dominant clonal population has been eradicated.

关键词： Squamous carcinoma oesophagus Barrett's oesophagus Radiofrequency ablation Squamous cell cancer High grade dysplasia

Quality of Life among Hong Kong Chinese Patients with Malignant Glioma

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Quality of Life among Hong Kong Chinese Patients with Malign...