The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model
Autor: | Rob Glynne-Jones, Frances M. Daley, J M A Northover, G. Atkin, S Bourne, George S. Wilson |
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Jazyk: | angličtina |
Rok vydání: | 2006 |
Předmět: |
Cancer Research
Pathology medicine.medical_specialty Cyclin A Transplantation Heterologous Mice SCID Thymidylate synthase Vascular occlusion Mice Ischemia Gene expression Dihydropyrimidine dehydrogenase medicine Biomarkers Tumor Animals Humans RNA Messenger Molecular Diagnostics biology hypoxia Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Thymidylate Synthase Prognosis Cell Hypoxia Gene expression profiling Transplantation Gene Expression Regulation Neoplastic Oncology biology.protein gene expression Immunohistochemistry Female medicine.symptom Colorectal Neoplasms |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 0007-0920 |
Popis: | Delays in tissue fixation following tumour vascular clamping and extirpation may adversely affect subsequent protein and mRNA analysis. This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase. Vascular occlusion of human tumour xenografts by D-shaped metal clamps permitted defined periods of tumour ischaemia. Alterations in protein expression were measured by immunohistochemistry and spectral imaging, and changes in mRNA were measured by reverse transcriptase–polymerase chain reaction. Thymidylate synthase expression decreased following vascular occlusion, and this correlated with cyclin A expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen. There were significant changes in the expression of several hypoxic markers, with carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels were also noted to change following tumour clamping. In this xenograft model, surgically induced tumour ischaemia considerably altered the gene expression profiles of several prognostic and hypoxic markers, suggesting that the degree of tumour ischaemia should be minimised prior to tissue fixation. |
Databáze: | OpenAIRE |
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