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Kinetics and regional specificity of irinotecan-induced gene expression in the gastrointestinal tract
- Source :
- Toxicology. 269:1-12
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Gastrointestinal toxicity remains a significant and dose-limiting complication of cancer treatment. While the pathophysiology is becoming clearer, considerable gaps in the knowledge remain surrounding the timing and site-specific gene changes which occur in response to insult. As such, this study aimed to assess gene expression profiles in a number of regions along the gastrointestinal tract following treatment with the chemotherapy agent, irinotecan, and correlate them with markers of cell death and tissue damage. Data analysis of microarray results found that genes involved in apoptosis, mitogen activated kinase (MAPK) signalling and inflammation were upregulated within 6 h, while genes involved in cell proliferation, wound healing and blood vessel formation were upregulated at later time points up to 72 h. Cell death was significantly increased at 6 and 24 h, and the stomach showed the lowest severity of overt tissue damage. Real time PCR of MAPK signalling pathway genes found that the jejunum and colon had significantly increased expression in a number of genes at 72 h, where as the stomach was unchanged. These results indicate that overall severity of tissue damage may be determined by precisely timed target gene responses specific to each region. Therapeutic targeting of key gene responses at the appropriate time point may prove to be effective for prevention of chemotherapy-induced gastrointestinal damage. Refereed/Peer-reviewed
- Subjects :
- MAPK/ERK pathway
Programmed cell death
Microarray
Medical Physiology
Inflammation
Biology
Irinotecan
Toxicology
gastrointestinal damage
Gene expression
medicine
Animals
rat
irinotecan
Oligonucleotide Array Sequence Analysis
Gastrointestinal tract
Kinase
Gene Expression Profiling
Pharmacology and Pharmaceutical Sciences
Rats
Gastrointestinal Tract
mucositis
Real-time polymerase chain reaction
Immunology
Cancer research
Camptothecin
Female
medicine.symptom
microarray
Signal Transduction
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 269
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....e04db87ae1ee4c4567595ee16bed5918