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dc.contributor.authorLi, Chenggang
dc.contributor.authorWilson, Philip B
dc.contributor.authorLevine, Edward
dc.contributor.authorBarber, Jim
dc.contributor.authorStewart, Alan L
dc.contributor.authorKumar, Shant
dc.date.accessioned2009-12-14T13:14:51Z
dc.date.available2009-12-14T13:14:51Z
dc.date.issued1999-04-20
dc.identifier.citationTGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. 1999, 84 (2):155-9 Int. J. Canceren
dc.identifier.issn0020-7136
dc.identifier.pmid10096248
dc.identifier.urihttp://hdl.handle.net/10541/87851
dc.description.abstractA serious complication of radiotherapy in the treatment of cancer patients is the late onset of fibrosis in normal tissues. Transforming growth factor beta (TGF-beta) is emerging as a key mediator of the fibrotic process through its effects on stimulation of fibroblast proliferation, migration and extracellular matrix (ECM) synthesis. The fact that radiation-induced vascular injury tends to precede the development of fibrosis has led to the suggestion that vascular damage is crucial in its pathogenesis. CD105, the specific type III vascular receptor for TGF-beta1 and -beta3, modulates cell proliferation and ECM production in response to TGF-beta in vitro. In this study, we have quantified the levels of TGF-beta1 and soluble CD105-TGF-beta1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2) breast cancer patients utilising an enhanced chemiluminescence ELISA system. During the follow-up period, 24 patients had developed moderate and one severe fibrosis of the breast. The mean TGF-beta1 level in these 25 patients was 203.2 +/- 37.3 pg/ml, which was significantly elevated above the level for those with no fibrosis. Furthermore, a significantly lower CD105-TGF-beta1 complex level was observed in the former compared to the latter. Spearman's correlation analysis showed that TGF-beta1 was positively correlated and the CD1O5-TGF-beta1 complex inversely correlated with the occurrence of breast fibrosis. Using a cut-off value of 96 pg/ml, the sensitivity and specificity of TGF-beta1 levels in predicting breast fibrosis were 76% and 74%, respectively. Our results indicate that TGF-beta1 and the receptor-ligand complex appear to be of clinical value in identifying patients at risk of developing post-radiotherapy fibrosis.
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshAdult
dc.subject.meshAntigens, CD
dc.subject.meshBiological Markers
dc.subject.meshBreast
dc.subject.meshBreast Neoplasms
dc.subject.meshEnzyme-Linked Immunosorbent Assay
dc.subject.meshFemale
dc.subject.meshFibrosis
dc.subject.meshHumans
dc.subject.meshImmunoblotting
dc.subject.meshMiddle Aged
dc.subject.meshReceptors, Cell Surface
dc.subject.meshReproducibility of Results
dc.subject.meshSensitivity and Specificity
dc.subject.meshTransforming Growth Factor beta
dc.subject.meshVascular Cell Adhesion Molecule-1
dc.titleTGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathological Sciences, Medical School, University of Manchester, UK.en
dc.identifier.journalInternational Journal of Cancer.en
html.description.abstractA serious complication of radiotherapy in the treatment of cancer patients is the late onset of fibrosis in normal tissues. Transforming growth factor beta (TGF-beta) is emerging as a key mediator of the fibrotic process through its effects on stimulation of fibroblast proliferation, migration and extracellular matrix (ECM) synthesis. The fact that radiation-induced vascular injury tends to precede the development of fibrosis has led to the suggestion that vascular damage is crucial in its pathogenesis. CD105, the specific type III vascular receptor for TGF-beta1 and -beta3, modulates cell proliferation and ECM production in response to TGF-beta in vitro. In this study, we have quantified the levels of TGF-beta1 and soluble CD105-TGF-beta1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2) breast cancer patients utilising an enhanced chemiluminescence ELISA system. During the follow-up period, 24 patients had developed moderate and one severe fibrosis of the breast. The mean TGF-beta1 level in these 25 patients was 203.2 +/- 37.3 pg/ml, which was significantly elevated above the level for those with no fibrosis. Furthermore, a significantly lower CD105-TGF-beta1 complex level was observed in the former compared to the latter. Spearman's correlation analysis showed that TGF-beta1 was positively correlated and the CD1O5-TGF-beta1 complex inversely correlated with the occurrence of breast fibrosis. Using a cut-off value of 96 pg/ml, the sensitivity and specificity of TGF-beta1 levels in predicting breast fibrosis were 76% and 74%, respectively. Our results indicate that TGF-beta1 and the receptor-ligand complex appear to be of clinical value in identifying patients at risk of developing post-radiotherapy fibrosis.


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