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C Verdelli Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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L Avagliano Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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P Creo Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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V Guarnieri Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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A Scillitani Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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L Vicentini Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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G B Steffano Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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E Beretta Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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L Soldati Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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E Costa Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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A Spada Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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G P Bulfamante Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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S Corbetta Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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important target for cancer therapy. Fibroblasts within the tumour stroma are critically involved in promoting tumour growth and angiogenesis through secretion of soluble factors, synthesis of extracellular matrix and direct cell–cell interaction. Tumour-associated

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Pedro Marques Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Sayka Barry Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Eivind Carlsen Department of Pathology, STHF, Skien, Norway

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David Collier Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Amy Ronaldson Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Sherine Awad Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Neil Dorward The National Hospital for Neurology and Neurosurgery, UCLH, NHS Trust, London, UK

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Joan Grieve The National Hospital for Neurology and Neurosurgery, UCLH, NHS Trust, London, UK

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Nigel Mendoza Department of Neurosurgery, Charing Cross Hospital, Imperial College, London, UK

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Samiul Muquit Department of Neurosurgery, Derriford Hospital, Plymouth, UK

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Ashley B Grossman Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Frances Balkwill Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK

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Márta Korbonits Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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fibroblasts undergo activation in tumours, often then termed as tumour-associated fibroblasts (TAFs) ( Cirri & Chiarugi 2012 , Shiga et al. 2015 ). TAFs are an important source of cytokines and growth factors which contribute to their pro-tumoural effects

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Xiang Zhang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Ya Hu Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Ming Cui Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Mengyi Wang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Xiaobin Li Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Yalu Zhang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Sen Yang Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Surong Hua Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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Meiping Shen Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Quan Liao Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

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profile the transcriptome of 27,251 cells isolated from 4 PA tissues. Our work revealed the cellular heterogeneity, transcriptional states, and immune cell diversity inside PA tissues, underlying the role of tumour-associated fibroblasts (TAFs) and immune

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Kathrin A Schmohl Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Andrea M Müller Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Alexandra Wechselberger Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Svenja Rühland Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany
Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Nicole Salb Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Nathalie Schwenk Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Heike Heuer Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Janette Carlsen Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Burkhard Göke Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany
Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Peter J Nelson Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Christine Spitzweg Department of Internal Medicine II, Medizinische Klinik und Poliklinik IV, Department of Biology II, Leibniz Institute for Environmental Medicine, Department of Nuclear Medicine, University Medical Center Hamburg‐Eppendorf, University Hospital of Munich, Munich, Germany

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Introduction Tumours are composed of malignant tumour cells and the ‘benign’ stromal compartment that contains many distinct cell types, including endothelial cells, smooth muscle cells, cells of the immune system and pericytes/cancer-associated

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J T W Kwon Department of Oncology, University of Oxford, Oxford, UK

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R J Bryant Department of Oncology, University of Oxford, Oxford, UK
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

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E E Parkes Department of Oncology, University of Oxford, Oxford, UK

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prognosis by virtue of the hypermutated tumour phenotype possessing a greater neoantigen load and in turn, being associated with increased immune infiltration ( Graham et al. 2020 ). Approval was predicated on the pooled analysis of patients enrolled

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Patsy S H Soon Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Edward Kim Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Cindy K Pon Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Anthony J Gill Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Katrina Moore Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Andrew J Spillane Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Diana E Benn Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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Robert C Baxter Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Northern Clinical School, South Western Sydney Clinical School, Department of Surgery, Endocrine and Oncology Surgery, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia

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fibroblasts, known as cancer-associated fibroblasts (CAFs), is important in tumour growth and progression ( Mueller & Fusenig 2004 ). These can be distinguished functionally from ‘normal’ fibroblasts in tissue distal from the tumour site. CAFs are believed to

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Wen G Jiang
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Gareth Watkins
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Oystein Fodstad
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Anthony Douglas-Jones
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Kefah Mokbel
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Robert E Mansel
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from our study concurs with a previous study by Xie et al. (2001 a ) on breast cancer in that Cyr61 is raised in breast tumours and is associated with aggressiveness of the tumours, including higher levels in NPI-3, nodal status, high grade, TNM-3

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W Imruetaicharoenchoke Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

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A Fletcher Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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W Lu Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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R J Watkins Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

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B Modasia Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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V L Poole Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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H R Nieto Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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R J Thompson Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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K Boelaert Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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M L Read Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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V E Smith Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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C J McCabe Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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have demonstrated that PBF is overexpressed in pituitary, thyroid, breast and colorectal tumours, and that upregulation of the gene is significantly associated with poorer oncological outcome in a range of tumours ( McCabe et al . 2003 , Stratford

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Patsy Soon Cancer Genetics, Department of Surgery, Department of Biochemistry, Hormones and Cancer, Kolling Institute of Medical Research, University of Sydney, Level 9, Kolling Building, Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia
Cancer Genetics, Department of Surgery, Department of Biochemistry, Hormones and Cancer, Kolling Institute of Medical Research, University of Sydney, Level 9, Kolling Building, Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia

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Hippokratis Kiaris Cancer Genetics, Department of Surgery, Department of Biochemistry, Hormones and Cancer, Kolling Institute of Medical Research, University of Sydney, Level 9, Kolling Building, Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia

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carcinogenesis ( Paland et al . 2009 ), cancer-associated fibroblasts (CAFs) create an environment that is conducive to tumour initiation and progression ( Olumi et al . 1999 , Hayward et al . 2001 , Orimo et al . 2005 , Soon et al . 2013 ). The

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W E Farrell Human Disease and Genomics Group, Institute of Science and Technology in Medicine, School of Medicine, Keele University, Stoke on Trent, Staffordshire ST4 7QB, UK

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tumourigenesis Considerable literature details the potential pathogenic changes in sporadic pituitary tumours that include hormones, growth factors, receptors, associated signal transduction pathways and cell-cycle regulators. A detailed consideration

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