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  1. Article: Pancreatic Cancer Organotypic Models.

    Coetzee, Abigail / Grose, Richard / Kocher, Hemant

    Current topics in microbiology and immunology

    2019  Volume 430, Page(s) 183–198

    Abstract: Pancreatic cancer has a dismal prognosis for patients due to late diagnosis and ineffective treatment options. There is a desperate need for more accurate disease models to enable improved therapies and diagnostic tests to reach the clinic. Pancreatic ... ...

    Abstract Pancreatic cancer has a dismal prognosis for patients due to late diagnosis and ineffective treatment options. There is a desperate need for more accurate disease models to enable improved therapies and diagnostic tests to reach the clinic. Pancreatic tumours have a high content of desmoplastic stroma, which forms a stiff, hypoxic tumour mass and contributes significantly to tumour development and metastatic spread. Therefore, 2D cell culture is not sufficient for understanding the complex biology of this disease. 3D in vitro models offer a more representative method of culturing cells for research in the laboratory. There are many different 3D models that can be used in research, organoids formed from patient or murine tumours are grown embedded in collagen or matrigel matrices, giving the potential for screening treatment options and personalised therapy in the future. Also, organotypic models using pancreatic cancer cell lines and stromal cells can be easily manipulated to study different aspects of pancreatic cancer and new therapeutic options in the laboratory. There are new emerging pancreatic cancer 3D models being developed, including microchip technology or synthetic scaffolds instead collagen and matrigel. All of these 3D culturing methods give an advantage over traditional 2D cell culture and could lead to improved understanding of this disease, translating to a better prognosis for patients in the clinic.
    MeSH term(s) Animals ; Cell Culture Techniques ; Humans ; Mice ; Pancreatic Neoplasms ; Stromal Cells
    Language English
    Publishing date 2019-02-16
    Publishing country Germany
    Document type Journal Article
    ISSN 0070-217X
    ISSN 0070-217X
    DOI 10.1007/82_2019_155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction: Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1.

    Coetzee, Abigail S / Carter, Edward P / Rodríguez-Fernández, Lucía / Heward, James / Wang, Qiaoying / Karim, Saadia A / Boughetane, Lina / Milton, Christopher / Uyulur, Firat / Morton, Jennifer P / Kocher, Hemant M / Grose, Richard P

    Oncogene

    2023  Volume 42, Issue 7, Page(s) 545

    Language English
    Publishing date 2023-01-10
    Publishing country England
    Document type Published Erratum
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-022-02557-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dissecting FGF Signalling to Target Cellular Crosstalk in Pancreatic Cancer.

    Carter, Edward P / Coetzee, Abigail S / Tomas Bort, Elena / Wang, Qiaoying / Kocher, Hemant M / Grose, Richard P

    Cells

    2021  Volume 10, Issue 4

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a 5 year survival rate of less than 8%, and is predicted to become the second leading cause of cancer-related death by 2030. Alongside late detection, which impacts upon surgical treatment, ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a 5 year survival rate of less than 8%, and is predicted to become the second leading cause of cancer-related death by 2030. Alongside late detection, which impacts upon surgical treatment, PDAC tumours are challenging to treat due to their desmoplastic stroma and hypovascular nature, which limits the effectiveness of chemotherapy and radiotherapy. Pancreatic stellate cells (PSCs), which form a key part of this stroma, become activated in response to tumour development, entering into cross-talk with cancer cells to induce tumour cell proliferation and invasion, leading to metastatic spread. We and others have shown that Fibroblast Growth Factor Receptor (FGFR) signalling can play a critical role in the interactions between PDAC cells and the tumour microenvironment, but it is clear that the FGFR signalling pathway is not acting in isolation. Here we describe our current understanding of the mechanisms by which FGFR signalling contributes to PDAC progression, focusing on its interaction with other pathways in signalling networks and discussing the therapeutic approaches that are being developed to try and improve prognosis for this terrible disease.
    MeSH term(s) Fibroblast Growth Factors/metabolism ; Humans ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatic Stellate Cells/metabolism ; Pancreatic Stellate Cells/pathology ; Receptors, Fibroblast Growth Factor/metabolism ; Signal Transduction
    Chemical Substances Receptors, Fibroblast Growth Factor ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2021-04-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10040847
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1.

    Coetzee, Abigail S / Carter, Edward P / Rodríguez-Fernández, Lucía / Heward, James / Wang, Qiaoying / Karim, Saadia A / Boughetane, Lina / Milton, Christopher / Uyulur, Firat / Morton, Jennifer P / Kocher, Hemant M / Grose, Richard P

    Oncogene

    2022  Volume 42, Issue 7, Page(s) 491–500

    Abstract: Pancreatic stellate cells (PSCs) are key to the treatment-refractory desmoplastic phenotype of pancreatic ductal adenocarcinoma (PDAC) and have received considerable attention as a stromal target for cancer therapy. This approach demands detailed ... ...

    Abstract Pancreatic stellate cells (PSCs) are key to the treatment-refractory desmoplastic phenotype of pancreatic ductal adenocarcinoma (PDAC) and have received considerable attention as a stromal target for cancer therapy. This approach demands detailed understanding of their pro- and anti-tumourigenic effects. Interrogating PSC-cancer cell interactions in 3D models, we identified nuclear FGFR1 as critical for PSC-led invasion of cancer cells. ChIP-seq analysis of FGFR1 in PSCs revealed a number of FGFR1 interaction sites within the genome, notably NRG1, which encodes the ERBB ligand Neuregulin. We show that nuclear FGFR1 regulates transcription of NRG1, which in turn acts in autocrine fashion through an ERBB2/4 heterodimer to promote invasion. In support of this, recombinant NRG1 in 3D model systems rescued the loss of invasion incurred by FGFR inhibition. In vivo we demonstrate that, while FGFR inhibition does not affect the growth of pancreatic tumours in mice, local invasion into the pancreas is reduced. Thus, FGFR and NRG1 may present new stromal targets for PDAC therapy.
    MeSH term(s) Mice ; Animals ; Up-Regulation ; Neuregulin-1/genetics ; Neuregulin-1/pharmacology ; Pancreatic Stellate Cells/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics
    Chemical Substances Neuregulin-1
    Language English
    Publishing date 2022-11-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-022-02513-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Validation of a Novel, Flash-Freezing Method: Aluminum Platform.

    Imrali, Ahmet / Hughes, Christine S / Coetzee, Abigail S / Delvecchio, Francesca R / Saad, Amina / Roberts, Rhiannon / Chelala, Claude / ChinAleong, Jo-Anne / Kocher, Hemant M

    Current protocols essential laboratory techniques

    2020  Volume 21, Issue 1, Page(s) e46

    Abstract: Stored biological materials should have minimal pre-analytical variations in order to provide researchers with high-quality samples that will give reliable and reproducible results, yet methods of storage should be easy to implement, with minimal cost ... ...

    Abstract Stored biological materials should have minimal pre-analytical variations in order to provide researchers with high-quality samples that will give reliable and reproducible results, yet methods of storage should be easy to implement, with minimal cost and health hazard. Frozen tissue samples are a valuable biological resource. Here we compare different methods, such as liquid nitrogen (LN) or dry ice (DI), to a cheap and safe alternative using an aluminum platform (AP). Murine fresh liver and pancreas tissues were used with varying lengths of warm ischemia time. Quality assessment was based on histological evaluation, DNA and RNA extraction and quantification, and RNA degradation analysis, as well preservation of antigens for immunofluorescence, in a blinded manner. Both in superficial and deep tissue sections, based on histological assessment, AP is superior to DI, or as good as LN techniques in terms of presence of ice crystals, cutting artifacts, and overall quality/structural preservation. DNA and RNA were successfully extracted in reasonable quantities from all freezing techniques, but RNA degradation was seen for pancreas samples across all techniques. Immunofluorescence with cytokeratin8 (CK-8), alpha smooth muscle actin (αSMA), CD3, and B220 shows equally good outcomes for AP and LN, which are better than DI. The aluminum platform is a cheap, yet reliable method to freeze samples, rapidly preserving histological, antigenic, and DNA/RNA quality. Wider testing is required across different sample types. © 2020 The Authors.
    Language English
    Publishing date 2020-11-25
    Publishing country United States
    Document type Journal Article
    ISSN 1948-3430
    ISSN 1948-3430
    DOI 10.1002/cpet.46
    Database MEDical Literature Analysis and Retrieval System OnLINE

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