Linked Life Data

17218636

Source:http://linkedlifedata.com/resource/pubmed/id/17218636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-22
pubmed:abstractText
Resistance of ovarian clear cell carcinoma (CCC) to platinum-based chemotherapy is associated with poor prognosis, and an effective treatment for advanced disease is urgently needed. HER2/neu is up-regulated more often in CCC than in other histologic types of epithelial ovarian cancer. The purpose of this study was to assess possible treatment for ovarian CCC with the anti-HER2 antibody trastuzumab or human adenovirus type 5 E1A. We treated 10 CCC cell lines with trastuzumab or E1A and assessed cell viability, proliferation, and colony formation and the expression of HER2 and wild-type p53 proteins and molecules downstream of those signaling pathways. HER2 protein was detected at various levels in all 10 cell lines by Western blotting and in 5 CCC cell lines by immunohistochemical staining; HER2 gene amplification was detected (by fluorescence in situ hybridization) in only one cell line (RMG-I). Trastuzumab did not inhibit proliferation in any of the four CCC cell lines tested (RMG-I, SKOV-2, OVTOKO, and OVSAYO). However, transfection with E1A (as compared with control vectors) reduced colony formation in all 10 CCC cell lines regardless of HER2 expression level. Infection of RMG-I and SMOV-2 cells with an adenoviral vector encoding E1A led to significant (P < 0.05) suppression of proliferation and enhancement of cell death; this effect required stabilization of p53 (but not p73) protein and was associated with the up-regulation of Bax and the cleavage of caspase-9. Other mechanisms, such as p53-independent apoptosis, may also be involved in E1A-mediated cell death in CCC. Finally, treatment with E1A prolonged survival in a CCC xenograft model (P < 0.001). E1A gene therapy, because of its ability to stabilize wild-type p53, is worth exploring as a treatment modality for women with ovarian CCC, which typically expresses wild-type p53.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
227-35
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17218636-Adenocarcinoma, Clear Cell, pubmed-meshheading:17218636-Adenovirus E1A Proteins, pubmed-meshheading:17218636-Animals, pubmed-meshheading:17218636-Antibodies, Monoclonal, pubmed-meshheading:17218636-Antibodies, Monoclonal, Humanized, pubmed-meshheading:17218636-Antineoplastic Agents, pubmed-meshheading:17218636-Cell Death, pubmed-meshheading:17218636-Cell Line, Tumor, pubmed-meshheading:17218636-Cell Proliferation, pubmed-meshheading:17218636-Female, pubmed-meshheading:17218636-Gene Therapy, pubmed-meshheading:17218636-Humans, pubmed-meshheading:17218636-Mice, pubmed-meshheading:17218636-Mice, SCID, pubmed-meshheading:17218636-Neoplastic Stem Cells, pubmed-meshheading:17218636-Ovarian Neoplasms, pubmed-meshheading:17218636-Receptor, erbB-2, pubmed-meshheading:17218636-Survival Analysis, pubmed-meshheading:17218636-Thermodynamics, pubmed-meshheading:17218636-Tumor Suppressor Protein p53, pubmed-meshheading:17218636-Xenograft Model Antitumor Assays
pubmed:year
2007
pubmed:articleTitle
Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential treatment strategy.
pubmed:affiliation
Department of Stem Cell Transplantation and Cellular Therapy, Unit 448, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural