Cited 10 times in
Circulating vascular endothelial growth factor receptor 2/pAkt-positive cells as a functional pharmacodynamic marker in metastatic colorectal cancers treated with antiangiogenic agent
DC Field | Value | Language |
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dc.contributor.author | 노재경 | - |
dc.contributor.author | 라선영 | - |
dc.contributor.author | 신상준 | - |
dc.contributor.author | 안중배 | - |
dc.contributor.author | 정현철 | - |
dc.contributor.author | 황지원 | - |
dc.date.accessioned | 2014-12-18T08:23:10Z | - |
dc.date.available | 2014-12-18T08:23:10Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/86208 | - |
dc.description.abstract | OBJECTIVE: The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for defining the optimum biological dose and schedule of bevacizumab administration against colon cancer in early clinical trials. METHODS: We evaluated inhibitory effects of bevacizumab on VEGF signaling and tumor growth in vitro and in vivo, and assessed phosphorylation of VEGF receptor 2 (VEGFR2) and downstream signaling in endothelial cells as pharmacodynamic markers using phospho-flow cytometry. We also validated markers in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based chemotherapy. RESULTS: In in vitro studies, bevacizumab inhibited proliferation of human umbilical vein endothelial cells in association with reduced VEGF signaling. Notably, bevacizumab inhibited VEGF-induced phosphorylation of VEGFR-2, Akt, and extracellular signal-regulated kinase (ERK). In vivo, treatment with bevacizumab inhibited growth of xenografted tumors and attenuated VEGF-induced phosphorylation of Akt and ERK. The median percentages of VEGFR2 + pAkt + and VEGFR2 + pERK + cells, determined by phospho-flow cytometry, were approximately 3-fold higher in mCRC patients than in healthy controls. Bevacizumab treatment decreased VEGFR2 + pAkt + cells in 18 of 24 patients on day 3. CONCLUSION: Bevacizumab combined with chemotherapy decreased the number of VEGFR2 + pAkt + cells, reflecting impaired VEGFR2 signaling. Together, these data suggest that changes in the proportion of circulating VEGFR2 + pAkt + cells may be a potential pharmacodynamic marker of the efficacy of antiangiogenic agents, and could prove valuable in determining drug dosage and administration schedule. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | INVESTIGATIONAL NEW DRUGS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Angiogenesis Inhibitors/pharmacology | - |
dc.subject.MESH | Angiogenesis Inhibitors/therapeutic use | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antibodies, Monoclonal, Humanized/pharmacology | - |
dc.subject.MESH | Antibodies, Monoclonal, Humanized/therapeutic use | - |
dc.subject.MESH | Bevacizumab | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Proliferation/drug effects | - |
dc.subject.MESH | Colorectal Neoplasms/drug therapy | - |
dc.subject.MESH | Colorectal Neoplasms/metabolism* | - |
dc.subject.MESH | Colorectal Neoplasms/pathology | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases/metabolism | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Human Umbilical Vein Endothelial Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/metabolism* | - |
dc.subject.MESH | Tumor Burden/drug effects | - |
dc.subject.MESH | Vascular Endothelial Growth Factor A | - |
dc.subject.MESH | Vascular Endothelial Growth Factor Receptor-2/metabolism* | - |
dc.subject.MESH | Xenograft Model Antitumor Assays | - |
dc.title | Circulating vascular endothelial growth factor receptor 2/pAkt-positive cells as a functional pharmacodynamic marker in metastatic colorectal cancers treated with antiangiogenic agent | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Sang Joon Shin | - |
dc.contributor.googleauthor | Jee Won Hwang | - |
dc.contributor.googleauthor | Joong Bae Ahn | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.contributor.googleauthor | Jae Kyung Roh | - |
dc.contributor.googleauthor | Hyun Cheol Chung | - |
dc.identifier.doi | 10.1007/s10637-012-9817-7 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01290 | - |
dc.contributor.localId | A02105 | - |
dc.contributor.localId | A02262 | - |
dc.contributor.localId | A03773 | - |
dc.contributor.localId | A04490 | - |
dc.contributor.localId | A01316 | - |
dc.relation.journalcode | J01184 | - |
dc.identifier.eissn | 1573-0646 | - |
dc.identifier.pmid | 22539090 | - |
dc.identifier.url | http://link.springer.com/article/10.1007%2Fs10637-012-9817-7 | - |
dc.subject.keyword | VEGFR2 | - |
dc.subject.keyword | Akt | - |
dc.subject.keyword | Bevacizumab | - |
dc.subject.keyword | Pharmacodynamic marker | - |
dc.subject.keyword | Phospho-flow cytometry | - |
dc.contributor.alternativeName | Roh, Jae Kyung | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.contributor.alternativeName | Shin, Sang Joon | - |
dc.contributor.alternativeName | Ahn, Joong Bae | - |
dc.contributor.alternativeName | Chung, Hyun Cheol | - |
dc.contributor.alternativeName | Hwang, Jee Won | - |
dc.contributor.affiliatedAuthor | Roh, Jae Kyung | - |
dc.contributor.affiliatedAuthor | Shin, Sang Joon | - |
dc.contributor.affiliatedAuthor | Ahn, Joong Bae | - |
dc.contributor.affiliatedAuthor | Chung, Hyun Cheol | - |
dc.contributor.affiliatedAuthor | Hwang, Jee Won | - |
dc.contributor.affiliatedAuthor | Rha, Sun Young | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 31 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 13 | - |
dc.identifier.bibliographicCitation | INVESTIGATIONAL NEW DRUGS, Vol.31(1) : 1-13, 2013 | - |
dc.identifier.rimsid | 28851 | - |
dc.type.rims | ART | - |
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