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Open AccessArticle

Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients

1
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
2
St. Vincent’s University Hospital, Dublin 4, Ireland
3
Trinity College Dublin, College Green, Dublin 2, Ireland
4
Department of Molecular Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland
5
Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA
6
St Luke’s Radiation Oncology Network, Dublin 6, Ireland
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(3), 962; https://doi.org/10.3390/ijms21030962
Received: 13 December 2019 / Revised: 28 January 2020 / Accepted: 29 January 2020 / Published: 31 January 2020
Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human pancreatic adenocarcinoma patients were implanted in severe combined immunodeficiency (SCID) mice. Samples from 78% of treatment-naïve pancreatic ductal adenocarcinoma patients grew as PDX tumours and were confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successfully passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human-specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from eight PDX tumours and where possible, corresponding primary tumour (T) and adjacent normal tissues (N). mRNA profiles of tumour vs. F1 PDX and normal vs. tumour were compared by Affymetrix microarray analysis. Differential gene expression showed over 5000 genes changed across the N vs. T and T vs. PDX samples. Gene ontology analysis of a subset of genes demonstrated genes upregulated in normal vs. tumour vs. PDX were linked with cell cycle, cycles cell process and mitotic cell cycle. Amongst the mRNA candidates elevated in the PDX and tumour vs. normal were SERPINB5, FERMT1, AGR2, SLC6A14 and TOP2A. These genes have been associated with growth, proliferation, invasion and metastasis in pancreatic cancer previously. Cumulatively, this demonstrates the applicability of PDX models and transcriptomic array to identify genes associated with growth and proliferation of pancreatic cancer. View Full-Text
Keywords: pancreatic cancer; patient-derived xenograft; microarray pancreatic cancer; patient-derived xenograft; microarray
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MDPI and ACS Style

Roche, S.; O’Neill, F.; Murphy, J.; Swan, N.; Meiller, J.; Conlon, N.T.; Geoghegan, J.; Conlon, K.; McDermott, R.; Rahman, R.; Toomey, S.; Straubinger, N.L.; Straubinger, R.M.; O’Connor, R.; McVey, G.; Moriarty, M.; Clynes, M. Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients. Int. J. Mol. Sci. 2020, 21, 962.

AMA Style

Roche S, O’Neill F, Murphy J, Swan N, Meiller J, Conlon NT, Geoghegan J, Conlon K, McDermott R, Rahman R, Toomey S, Straubinger NL, Straubinger RM, O’Connor R, McVey G, Moriarty M, Clynes M. Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients. International Journal of Molecular Sciences. 2020; 21(3):962.

Chicago/Turabian Style

Roche, Sandra; O’Neill, Fiona; Murphy, Jean; Swan, Niall; Meiller, Justine; Conlon, Neil T.; Geoghegan, Justin; Conlon, Kevin; McDermott, Ray; Rahman, Rozana; Toomey, Sinead; Straubinger, Ninfa L.; Straubinger, Robert M.; O’Connor, Robert; McVey, Gerard; Moriarty, Michael; Clynes, Martin. 2020. "Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients" Int. J. Mol. Sci. 21, no. 3: 962.

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