Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85562
Title:
Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation.
Authors:
Chan, K C; Knox, W F; Gandhi, A; Slamon, D J; Potten, Christopher S; Bundred, Nigel J
Abstract:
BACKGROUND: Ductal carcinoma in situ (DCIS) expresses c-erbB-2 receptor and epidermal growth factor receptor (EGFR). The aim of this study was to determine whether blocking of c-erbB-2 receptor with a humanized monoclonal antibody, 4D5 (HerceptinTM), or of EGFR with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (IressaTM), would decrease epithelial proliferation in DCIS. METHODS: DCIS tissue from 18 women undergoing surgery was implanted into 16 to 20 athymic nude mice per experiment (eight xenografts per mouse). Treatment commenced 2 weeks after implantation and consisted either of twice-weekly intraperitoneal injections of 4D5 10 mg/kg or of daily gavage with ZD1839 at 100-200 mg/kg for 14 days; appropriate controls were included. Xenografts were removed on days 14, 21 and 28. Proliferation was assessed by counting 1000 epithelial cells after Ki67 immuno- staining. RESULTS: ZD1839 inhibited proliferation compared with that in controls after 14 days (P < 0.01), whereas 4D5 did not. CONCLUSION: Proliferation in DCIS was decreased by EGFR tyrosine kinase inhibition but not by c-erbB-2 receptor blockade. ZD1839, an orally active and selective EGFR-TKI, has potential as adjuvant therapy in DCIS.
Affiliation:
Department of Surgery, University Hospital of South Manchester, Manchester, UK.
Citation:
Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation. 2001, 88 (3):412-8 Br J Surg
Journal:
The British Journal of Surgery
Issue Date:
Mar-2001
URI:
http://hdl.handle.net/10541/85562
DOI:
10.1046/j.1365-2168.2001.01686.x
PubMed ID:
11260109
Type:
Article
Language:
en
ISSN:
0007-1323
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorChan, K Cen
dc.contributor.authorKnox, W Fen
dc.contributor.authorGandhi, Aen
dc.contributor.authorSlamon, D Jen
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorBundred, Nigel Jen
dc.date.accessioned2009-11-06T14:37:16Z-
dc.date.available2009-11-06T14:37:16Z-
dc.date.issued2001-03-
dc.identifier.citationBlockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation. 2001, 88 (3):412-8 Br J Surgen
dc.identifier.issn0007-1323-
dc.identifier.pmid11260109-
dc.identifier.doi10.1046/j.1365-2168.2001.01686.x-
dc.identifier.urihttp://hdl.handle.net/10541/85562-
dc.description.abstractBACKGROUND: Ductal carcinoma in situ (DCIS) expresses c-erbB-2 receptor and epidermal growth factor receptor (EGFR). The aim of this study was to determine whether blocking of c-erbB-2 receptor with a humanized monoclonal antibody, 4D5 (HerceptinTM), or of EGFR with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (IressaTM), would decrease epithelial proliferation in DCIS. METHODS: DCIS tissue from 18 women undergoing surgery was implanted into 16 to 20 athymic nude mice per experiment (eight xenografts per mouse). Treatment commenced 2 weeks after implantation and consisted either of twice-weekly intraperitoneal injections of 4D5 10 mg/kg or of daily gavage with ZD1839 at 100-200 mg/kg for 14 days; appropriate controls were included. Xenografts were removed on days 14, 21 and 28. Proliferation was assessed by counting 1000 epithelial cells after Ki67 immuno- staining. RESULTS: ZD1839 inhibited proliferation compared with that in controls after 14 days (P < 0.01), whereas 4D5 did not. CONCLUSION: Proliferation in DCIS was decreased by EGFR tyrosine kinase inhibition but not by c-erbB-2 receptor blockade. ZD1839, an orally active and selective EGFR-TKI, has potential as adjuvant therapy in DCIS.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCancer Transplantationen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCarcinoma, Ductal, Breast-
dc.subject.meshCell Division-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshQuinazolines-
dc.subject.meshReceptor, Epidermal Growth Factor-
dc.subject.meshReceptor, erbB-2-
dc.subject.meshTransplantation, Heterologous-
dc.subject.meshTumor Cells, Cultured-
dc.titleBlockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation.en
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, University Hospital of South Manchester, Manchester, UK.en
dc.identifier.journalThe British Journal of Surgeryen
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