Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.
Aged
Aged, 80 and over
Amino Acid Transport Systems
/ genetics
Animals
Carcinoma, Pancreatic Ductal
/ genetics
Cell Culture Techniques
Cell Line, Tumor
Cell Proliferation
DNA Topoisomerases, Type II
/ genetics
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Male
Membrane Proteins
/ genetics
Mice
Mice, SCID
Middle Aged
Mucoproteins
/ genetics
Neoplasm Proteins
/ genetics
Neoplasm Transplantation
Oligonucleotide Array Sequence Analysis
Oncogene Proteins
/ genetics
Pancreatic Neoplasms
/ genetics
Poly-ADP-Ribose Binding Proteins
/ genetics
Serpins
/ genetics
microarray
pancreatic cancer
patient-derived xenograft
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
31 Jan 2020
31 Jan 2020
Historique:
received:
13
12
2019
revised:
28
01
2020
accepted:
29
01
2020
entrez:
7
2
2020
pubmed:
7
2
2020
medline:
18
11
2020
Statut:
epublish
Résumé
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
Identifiants
pubmed: 32024004
pii: ijms21030962
doi: 10.3390/ijms21030962
pmc: PMC7037178
pii:
doi:
Substances chimiques
AGR2 protein, human
0
Amino Acid Transport Systems
0
FERMT1 protein, human
0
Membrane Proteins
0
Mucoproteins
0
Neoplasm Proteins
0
Oncogene Proteins
0
Poly-ADP-Ribose Binding Proteins
0
SERPIN-B5
0
SLC6A14 protein, human
0
Serpins
0
DNA Topoisomerases, Type II
EC 5.99.1.3
TOP2A protein, human
EC 5.99.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Science Foundation Ireland
ID : SFI/14/US/B2997
Pays : Ireland
Organisme : St Luke's Institute for Cancer Research
ID : Radiation Biology and Proteomics of Pancreatic Cancer
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest
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