Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors
RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based ap...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group
2012
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| _version_ | 1797099790295629824 |
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| author | Olsen, A Davies, J Medley, L Breen, D Talbot, D McHugh, P |
| author_facet | Olsen, A Davies, J Medley, L Breen, D Talbot, D McHugh, P |
| author_sort | Olsen, A |
| collection | OXFORD |
| description | RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies. |
| first_indexed | 2024-03-07T05:28:37Z |
| format | Journal article |
| id | oxford-uuid:e16bab86-fae4-4986-b292-26e3aee19ec7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:28:37Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:e16bab86-fae4-4986-b292-26e3aee19ec72022-03-27T09:54:23ZQuantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung TumorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e16bab86-fae4-4986-b292-26e3aee19ec7EnglishSymplectic Elements at OxfordNature Publishing Group2012Olsen, ADavies, JMedley, LBreen, DTalbot, DMcHugh, PRNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies. |
| spellingShingle | Olsen, A Davies, J Medley, L Breen, D Talbot, D McHugh, P Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors |
| title | Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors |
| title_full | Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors |
| title_fullStr | Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors |
| title_full_unstemmed | Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors |
| title_short | Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors |
| title_sort | quantitative analysis of survivin protein expression and its therapeutic depletion by an antisense oligonucleotide in human lung tumors |
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