| Synergistic antitumor effects of HER2/neu antisense oligodeoxynucleotides and conventional chemotherapeutic agents. | |
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MedLine Citation:
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PMID: 10455915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The HER2/neu oncogene is overexpressed in a substantial fraction of human tumors. HER2/neu overexpressing tumors may be intrinsically resistant to chemotherapy. The present study examined the ability of antisense-mediated downregulation of HER2/neu expression to enhance the antitumor effects of conventional chemotherapeutic agents against human tumor cells that overexpress HER2/neu. METHODS: The effects of HER2/neu antisense oligodeoxynucleotides (ODNs) on the growth inhibitory and proapoptotic activity of several distinct chemotherapeutic agents were examined in vitro. In vivo effects of HER2/neu antisense ODNs in combination with doxorubicin hydrochloride were assessed by examining the growth of human tumor xenografts implanted into nude mice. RESULTS: The proliferation of tumor cell lines that overexpress HER2/neu was inhibited by antisense ODNs in combination with conventional chemotherapeutic agents in an additive or synergistic fashion. Such combination therapy also demonstrated synergistic activation of apoptosis. HER2/neu antisense ODNs in combination with doxorubicin hydrochloride demonstrated synergistic antitumor effects in vivo as well. CONCLUSIONS: Downregulation of HER2/neu expression can enhance the sensitivity of human cancer cells, which overexpress HER2/neu to the cytotoxic effects of chemotherapy. Antisense ODNs targeting the HER2/neu gene may play a role in cancer therapy. |
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Authors:
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H Roh; C B Hirose; C B Boswell; J A Pippin; J A Drebin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Surgery Volume: 126 ISSN: 0039-6060 ISO Abbreviation: Surgery Publication Date: 1999 Aug |
Date Detail:
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Created Date: 1999-09-02 Completed Date: 1999-09-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0417347 Medline TA: Surgery Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 413-21 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects Down-Regulation Doxorubicin / pharmacology Drug Synergism Female Humans Mice Mice, Nude Oligonucleotides, Antisense / pharmacology* Receptor, erbB-2 / antagonists & inhibitors* Tamoxifen / pharmacology Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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T32CA09621/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Oligonucleotides, Antisense; 10540-29-1/Tamoxifen; 23214-92-8/Doxorubicin; EC 2.7.10.1/Receptor, erbB-2 |
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