Comparison of the cellular molecular stress responses after treatments used in bladder cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/81241
Title:
Comparison of the cellular molecular stress responses after treatments used in bladder cancer.
Authors:
Shackley, David C; Haylett, A; Whitehurst, Colin; Betts, C D; O'Flynn, K; Clarke, Noel W ( 0000-0001-7776-8059 ) ; Moore, James V
Abstract:
OBJECTIVE: To investigate the molecular stress responses related to the quality of recovery of normal tissue after various treatments for bladder cancer, i.e. hyperthermia, ionizing radiation, mitomycin-C and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). MATERIALS AND METHODS: The study focused particularly on intracellular fibroblast levels of heat-shock protein-47 (HSP47) and HSP72, which are associated with collagen metabolism and the development of tolerance to repeated treatment, respectively. Iso-effective treatment doses (50% clonogenic cell survival) of each method were delivered to a 3T6 murine fibroblast model. Intracellular extracts were analysed at 3, 6, 9, 12 and 24 h after treatment, using Western blot analysis to compare the levels of HSP47 and HSP72. Time-matched treatment and control groups were quantified by comparison with actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression using appropriate software. RESULTS: There were various changes in levels of HSP expression with treatment method; HSP47 levels were significantly higher after hyperthermia and radiation but not with mitomycin-C or ALA-PDT. HSP72 levels were significantly higher with all methods except ALA-PDT. CONCLUSIONS: Hyperthermia and ionizing radiation are associated with early increases in levels of HSP47 (a marker of collagen metabolism), in contrast to ALA-PDT and mitomycin-C. These findings are compatible with clinical findings where fibrosis/scarring is common with the first two but not the last two methods. In addition, all methods except ALA-PDT are associated with an increase in HSP 72 (a protein associated with cellular tolerance) and this may help to explain, at a cellular level, why resistance to repeated ALA-PDT treatments does not seem to occur.
Affiliation:
CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Manchester, UK. Daveshackley@hotmail.com
Citation:
Comparison of the cellular molecular stress responses after treatments used in bladder cancer. 2002, 90 (9):924-32 BJU Int.
Journal:
BJU International
Issue Date:
Dec-2002
URI:
http://hdl.handle.net/10541/81241
PubMed ID:
12460358
Type:
Article
Language:
en
ISSN:
1464-4096
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorShackley, David C-
dc.contributor.authorHaylett, A-
dc.contributor.authorWhitehurst, Colin-
dc.contributor.authorBetts, C D-
dc.contributor.authorO'Flynn, K-
dc.contributor.authorClarke, Noel W-
dc.contributor.authorMoore, James V-
dc.date.accessioned2009-09-16T10:28:10Z-
dc.date.available2009-09-16T10:28:10Z-
dc.date.issued2002-12-
dc.identifier.citationComparison of the cellular molecular stress responses after treatments used in bladder cancer. 2002, 90 (9):924-32 BJU Int.en
dc.identifier.issn1464-4096-
dc.identifier.pmid12460358-
dc.identifier.urihttp://hdl.handle.net/10541/81241-
dc.description.abstractOBJECTIVE: To investigate the molecular stress responses related to the quality of recovery of normal tissue after various treatments for bladder cancer, i.e. hyperthermia, ionizing radiation, mitomycin-C and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). MATERIALS AND METHODS: The study focused particularly on intracellular fibroblast levels of heat-shock protein-47 (HSP47) and HSP72, which are associated with collagen metabolism and the development of tolerance to repeated treatment, respectively. Iso-effective treatment doses (50% clonogenic cell survival) of each method were delivered to a 3T6 murine fibroblast model. Intracellular extracts were analysed at 3, 6, 9, 12 and 24 h after treatment, using Western blot analysis to compare the levels of HSP47 and HSP72. Time-matched treatment and control groups were quantified by comparison with actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression using appropriate software. RESULTS: There were various changes in levels of HSP expression with treatment method; HSP47 levels were significantly higher after hyperthermia and radiation but not with mitomycin-C or ALA-PDT. HSP72 levels were significantly higher with all methods except ALA-PDT. CONCLUSIONS: Hyperthermia and ionizing radiation are associated with early increases in levels of HSP47 (a marker of collagen metabolism), in contrast to ALA-PDT and mitomycin-C. These findings are compatible with clinical findings where fibrosis/scarring is common with the first two but not the last two methods. In addition, all methods except ALA-PDT are associated with an increase in HSP 72 (a protein associated with cellular tolerance) and this may help to explain, at a cellular level, why resistance to repeated ALA-PDT treatments does not seem to occur.en
dc.language.isoenen
dc.subjectUrinary Bladder Canceren
dc.subjectCultured Tumour Cellsen
dc.subject.meshAnimals-
dc.subject.meshAntibiotics, Antineoplastic-
dc.subject.meshBlotting, Western-
dc.subject.meshCollagen-
dc.subject.meshHSP47 Heat-Shock Proteins-
dc.subject.meshHSP72 Heat-Shock Proteins-
dc.subject.meshHeat-Shock Proteins-
dc.subject.meshHyperthermia, Induced-
dc.subject.meshMice-
dc.subject.meshMitomycin-
dc.subject.meshPhotochemotherapy-
dc.subject.meshStress, Physiological-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshUrinary Bladder Neoplasms-
dc.titleComparison of the cellular molecular stress responses after treatments used in bladder cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Manchester, UK. Daveshackley@hotmail.comen
dc.identifier.journalBJU Internationalen
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