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https://hdl.handle.net/2440/17444
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dc.contributor.author | Bowen, J. | - |
dc.contributor.author | Gibson, R. | - |
dc.contributor.author | Keefe, D. | - |
dc.contributor.author | Cummins, A. | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Pathology, 2005; 37(1):56-62 | - |
dc.identifier.issn | 0031-3025 | - |
dc.identifier.issn | 1465-3931 | - |
dc.identifier.uri | http://hdl.handle.net/2440/17444 | - |
dc.description.abstract | Aims: Small intestinal crypt cells rapidly undergo apoptosis in response to cytotoxic drug treatment that results in gastrointestinal toxicity. The Bcl-2 family have been implicated in both positive and negative regulation of intestinal cell apoptosis. The aim of this study was to examine the effect of cytotoxic treatment on Bcl-2 protein expression in patients and rats with tumours. Methods: Four pro- and four anti-apoptotic members of the Bcl-2 family, caspase-3 and p53 were examined in small intestinal crypts before and after treatment in rats and humans. Immunohistochemistry identified changes in protein expression over time, while relative RT-PCR was used to investigate mRNA expression in rat small intestine. Results: Cytotoxic treatment increased p53 and caspase-3 which coincided with elevated levels of apoptosis. Bax and Bak protein and mRNA expression also significantly increased at 6 hours following treatment in rats. Bax and Bak protein increased at day 1 after treatment in humans. Anti-apoptotic Mcl-1 protein decreased within 24 hours. Other Bcl-2 family members showed only modest changes. Conclusion: Increased expression of Bax and Bak but not other Bcl-2 family members is associated with apoptosis in small intestinal crypts and may amplify the sensitivity and susceptibility of crypt cells to chemotherapy-induced enteropathy. | - |
dc.description.statementofresponsibility | Joanne M. Bowen; Rachel J. Gibson; Dorothy M. Keefe; Adrian G. Cummins | - |
dc.language.iso | en | - |
dc.publisher | Taylor & Francis | - |
dc.source.uri | http://dx.doi.org/10.1080/00313020400023461 | - |
dc.subject | Intestinal Mucosa | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Rats | - |
dc.subject | Intestinal Neoplasms | - |
dc.subject | Caspases | - |
dc.subject | Membrane Proteins | - |
dc.subject | Proto-Oncogene Proteins c-bcl-2 | - |
dc.subject | RNA, Messenger | - |
dc.subject | Antineoplastic Agents | - |
dc.subject | Immunohistochemistry | - |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject | Apoptosis | - |
dc.subject | Female | - |
dc.subject | Tumor Suppressor Protein p53 | - |
dc.subject | bcl-2 Homologous Antagonist-Killer Protein | - |
dc.subject | bcl-2-Associated X Protein | - |
dc.subject | Caspase 3 | - |
dc.title | Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1080/00313020400023461 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Bowen, J. [0000-0003-0876-0031] | - |
dc.identifier.orcid | Gibson, R. [0000-0002-4796-1621] | - |
dc.identifier.orcid | Keefe, D. [0000-0001-9377-431X] | - |
dc.identifier.orcid | Cummins, A. [0000-0003-3115-9498] | - |
Appears in Collections: | Aurora harvest 6 Medicine publications |
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