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Pancreatic Neoplasms: HELP
Articles by Mariska Miranda
Based on 1 article published since 2010
(Why 1 article?)
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Between 2010 and 2020, Mariska Miranda wrote the following article about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Gemcitabine and CHK1 inhibition potentiate EGFR-directed radioimmunotherapy against pancreatic ductal adenocarcinoma. 2014

Al-Ejeh, Fares / Pajic, Marina / Shi, Wei / Kalimutho, Murugan / Miranda, Mariska / Nagrial, Adnan M / Chou, Angela / Biankin, Andrew V / Grimmond, Sean M / Anonymous4220794 / Brown, Michael P / Khanna, Kum Kum. ·Authors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research; St Vincent's Clinical School, Faculty of Medicine, University of NSW; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, New South Wales; Australian Pancreatic Cancer Genome Initiative, for the full list of contributors see http://www.pancreaticcancer.net.au/apgi/collaborators; Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, and Centre for Cancer Biology, SA Pathology; School of Medicine, University of Adelaide, Adelaide, Australia; and Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom Fares.Al-Ejeh@qimrberghofer.edu.au. · Authors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research; St Vincent's Clinical School, Faculty of Medicine, University of NSW; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, New South Wales; Australian Pancreatic Cancer Genome Initiative, for the full list of contributors see http://www.pancreaticcancer.net.au/apgi/collaborators; Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, and Centre for Cancer Biology, SA Pathology; School of Medicine, University of Adelaide, Adelaide, Australia; and Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United KingdomAuthors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research; St Vincent's Clinical School, Faculty of Medicine, University of NSW; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, New South Wales; Australian Pancreatic Cancer Genome Initiative, for the full list of contributors see http://www.pancreaticcancer.net.au/apgi/collaborators; Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, and Centre for Cancer Biology, SA Pathology; School of Medicine, University of Adelaide, Adelaide, Australia; and Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · Authors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research; St Vincent's Clinical School, Faculty of Medicine, University of NSW; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, New South Wales; Australian Pancreatic Cancer Genome Initiative, for the full list of contributors see http://www.pancreaticcancer.net.au/apgi/collaborators; Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, and Centre for Cancer Biology, SA Pathology; School of Medicine, University of Adelaide, Adelaide, Australia; and Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · Authors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research; St Vincent's Clinical School, Faculty of Medicine, University of NSW; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, New South Wales; Australian Pancreatic Cancer Genome Initiative, for the full list of contributors see http://www.pancreaticcancer.net.au/apgi/collaborators; Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, and Centre for Cancer Biology, SA Pathology; School of Medicine, University of Adelaide, Adelaide, Australia; and Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United KingdomAuthors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research; St Vincent's Clinical School, Faculty of Medicine, University of NSW; Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, New South Wales; Australian Pancreatic Cancer Genome Initiative, for the full list of contributors see http://www.pancreaticcancer.net.au/apgi/collaborators; Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, and Centre for Cancer Biology, SA Pathology; School of Medicine, University of Adelaide, Adelaide, Australia; and Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United KingdomAuthors' Affiliations: Signal Transduction Laboratory, QIMR Berghofer Medical Research Institute, Herston; Queensland Centre for Medic ·Clin Cancer Res · Pubmed #24838526.

ABSTRACT: PURPOSE: To develop effective combination therapy against pancreatic ductal adenocarcinoma (PDAC) with a combination of chemotherapy, CHK1 inhibition, and EGFR-targeted radioimmunotherapy. EXPERIMENTAL DESIGN: Maximum tolerated doses were determined for the combination of gemcitabine, the CHK1 inhibitor PF-477736, and Lutetium-177 ((177)Lu)-labeled anti-EGFR antibody. This triple combination therapy was investigated using PDAC models from well-established cell lines, recently established patient-derived cell lines, and fresh patient-derived xenografts. Tumors were investigated for the accumulation of (177)Lu-anti-EGFR antibody, survival of tumor-initiating cells, induction of DNA damage, cell death, and tumor tissue degeneration. RESULTS: The combination of gemcitabine and CHK1 inhibitor PF-477736 with (177)Lu-anti-EGFR antibody was tolerated in mice. This triplet was effective in established tumors and prevented the recurrence of PDAC in four cell line-derived and one patient-derived xenograft model. This exquisite response was associated with the loss of tumor-initiating cells as measured by flow cytometric analysis and secondary implantation of tumors from treated mice into treatment-naïve mice. Extensive DNA damage, apoptosis, and tumor degeneration were detected in the patient-derived xenograft. Mechanistically, we observed CDC25A stabilization as a result of CHK1 inhibition with consequent inhibition of gemcitabine-induced S-phase arrest as well as a decrease in canonical (ERK1/2 phosphorylation) and noncanonical EGFR signaling (RAD51 degradation) as a result of EGFR inhibition. CONCLUSIONS: Our study developed an effective combination therapy against PDAC that has potential in the treatment of PDAC.