| Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response. | |
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MedLine Citation:
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PMID: 21036697 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Oblimersen, an ODN targeting BCL-2 RNA, has been shown to be effective in reducing BCL-2 expression in vitro and in in vivo models engineered to overexpress BCL-2. The present study evaluated the efficacy of combining BCL-2 ODN and radiation in small-cell lung cancers (SCLC) cell lines. MATERIALS AND METHODS: The in vitro effect was determined using short term (cell viability) and long term (clonogenic) assays. Apoptosis, BCL-2 expression and intratumoural uptake of the FAM-ODN with or without prior radiation treatment were also evaluated. Combination of ODN and RT was also assessed in vivo. RESULTS: Radiation was shown to increase intracellular and intratumoural penetration of oblimersen, confirming previous results obtained in prostate cancer xenograft models. Oblimersen decreased BCL-2 protein expression in vitro and in vivo. BCL-2 ODN sensitised H69 cells to radiation in vitro and in vivo. Oblimersen increased radiation-induced apoptosis and decreased in vivo tumoural vascularisation. CONCLUSION: Oblimersen was shown to increase in vitro and in vivo effect of RT on SCLC cell lines. Radiation increases intracellular and intratumoural penetration of ODN. This pre-clinical study argues in favour of clinical development in localised SCLC. |
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Authors:
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Yohann Loriot; Pierre Mordant; Bob D Brown; Jean Bourhis; Jean-Charles Soria; Eric Deutsch |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Anticancer research Volume: 30 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-12-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 3869-78 Citation Subset: IM |
Affiliation:
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UPRES 27-10, Institut Gustave Roussy, Villejuif, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, genetics, radiation effects Carcinoma, Small Cell / genetics, metabolism, radiotherapy, therapy Cell Line, Tumor Cell Survival / drug effects, genetics, radiation effects Combined Modality Therapy Female Humans Lung Neoplasms / genetics, metabolism, radiotherapy, therapy* Mice Mice, Nude Oligonucleotides, Antisense / genetics, pharmacokinetics, pharmacology* Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*, biosynthesis, genetics Thionucleotides / genetics, pharmacokinetics, pharmacology* Xenograft Model Antitumor Assays |
| Chemical | |
Reg. No./Substance:
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0/Oligonucleotides, Antisense; 0/Proto-Oncogene Proteins c-bcl-2; 0/Thionucleotides; 0/oblimersen |
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