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Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells
by
De, A
, Sadiq, A
, Thumma, S C
, Patel, M R
, Jacobson, B A
, Franklin, M J
, Konicek, B W
, Jay-Dixon, J
, Graff, J R
, Kratzke, R A
in
13
/ 13/1
/ 13/106
/ 13/109
/ 13/2
/ 38/1
/ 42/109
/ 631/67/1612/1350
/ 692/308
/ 82/1
/ 82/80
/ 96
/ 96/2
/ Actin
/ Antisense oligonucleotides
/ Biomedical and Life Sciences
/ Biomedicine
/ c-Myc protein
/ Cancer research
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Cell Line, Tumor
/ Cell proliferation
/ Cell Proliferation - drug effects
/ Cell Proliferation - genetics
/ Chemotherapy
/ Clinical trials
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - pharmacology
/ Development and progression
/ Dose-Response Relationship, Drug
/ Eukaryotic Initiation Factor-4E - genetics
/ Eukaryotic Initiation Factor-4E - metabolism
/ Gemcitabine
/ Gene Expression
/ Gene Therapy
/ Genetic aspects
/ Genetic research
/ Humans
/ Initiation factor eIF-4E
/ Lung cancer
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - genetics
/ Malignancy
/ Molecular Targeted Therapy - methods
/ Myc protein
/ Non-small cell lung cancer
/ Non-small cell lung carcinoma
/ Oligonucleotides, Antisense - genetics
/ Oligonucleotides, Antisense - pharmacology
/ Oncogenes
/ original-article
/ Osteopontin
/ Osteopontin - metabolism
/ Properties
/ Small cell lung carcinoma
/ Translation (Genetics)
/ Vascular endothelial growth factor
/ Vascular Endothelial Growth Factor A - metabolism
2015
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Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells
by
De, A
, Sadiq, A
, Thumma, S C
, Patel, M R
, Jacobson, B A
, Franklin, M J
, Konicek, B W
, Jay-Dixon, J
, Graff, J R
, Kratzke, R A
in
13
/ 13/1
/ 13/106
/ 13/109
/ 13/2
/ 38/1
/ 42/109
/ 631/67/1612/1350
/ 692/308
/ 82/1
/ 82/80
/ 96
/ 96/2
/ Actin
/ Antisense oligonucleotides
/ Biomedical and Life Sciences
/ Biomedicine
/ c-Myc protein
/ Cancer research
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Cell Line, Tumor
/ Cell proliferation
/ Cell Proliferation - drug effects
/ Cell Proliferation - genetics
/ Chemotherapy
/ Clinical trials
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - pharmacology
/ Development and progression
/ Dose-Response Relationship, Drug
/ Eukaryotic Initiation Factor-4E - genetics
/ Eukaryotic Initiation Factor-4E - metabolism
/ Gemcitabine
/ Gene Expression
/ Gene Therapy
/ Genetic aspects
/ Genetic research
/ Humans
/ Initiation factor eIF-4E
/ Lung cancer
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - genetics
/ Malignancy
/ Molecular Targeted Therapy - methods
/ Myc protein
/ Non-small cell lung cancer
/ Non-small cell lung carcinoma
/ Oligonucleotides, Antisense - genetics
/ Oligonucleotides, Antisense - pharmacology
/ Oncogenes
/ original-article
/ Osteopontin
/ Osteopontin - metabolism
/ Properties
/ Small cell lung carcinoma
/ Translation (Genetics)
/ Vascular endothelial growth factor
/ Vascular Endothelial Growth Factor A - metabolism
2015
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Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells
by
De, A
, Sadiq, A
, Thumma, S C
, Patel, M R
, Jacobson, B A
, Franklin, M J
, Konicek, B W
, Jay-Dixon, J
, Graff, J R
, Kratzke, R A
in
13
/ 13/1
/ 13/106
/ 13/109
/ 13/2
/ 38/1
/ 42/109
/ 631/67/1612/1350
/ 692/308
/ 82/1
/ 82/80
/ 96
/ 96/2
/ Actin
/ Antisense oligonucleotides
/ Biomedical and Life Sciences
/ Biomedicine
/ c-Myc protein
/ Cancer research
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Cell Line, Tumor
/ Cell proliferation
/ Cell Proliferation - drug effects
/ Cell Proliferation - genetics
/ Chemotherapy
/ Clinical trials
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - pharmacology
/ Development and progression
/ Dose-Response Relationship, Drug
/ Eukaryotic Initiation Factor-4E - genetics
/ Eukaryotic Initiation Factor-4E - metabolism
/ Gemcitabine
/ Gene Expression
/ Gene Therapy
/ Genetic aspects
/ Genetic research
/ Humans
/ Initiation factor eIF-4E
/ Lung cancer
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - genetics
/ Malignancy
/ Molecular Targeted Therapy - methods
/ Myc protein
/ Non-small cell lung cancer
/ Non-small cell lung carcinoma
/ Oligonucleotides, Antisense - genetics
/ Oligonucleotides, Antisense - pharmacology
/ Oncogenes
/ original-article
/ Osteopontin
/ Osteopontin - metabolism
/ Properties
/ Small cell lung carcinoma
/ Translation (Genetics)
/ Vascular endothelial growth factor
/ Vascular Endothelial Growth Factor A - metabolism
2015
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Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells
Journal Article
Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances chemosensitivity of non-small-cell lung cancer cells
2015
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Overview
Elevated levels of eukaryotic translation initiation factor 4E (eIF4E) enhance translation of many malignancy-related proteins, such as vascular endothelial growth factor (VEGF), c-Myc and osteopontin. In non-small-cell lung cancer (NSCLC), levels of eIF4E are significantly increased compared with normal lung tissue. Here, we used an antisense oligonucleotide (ASO) to inhibit the expression of eIF4E in NSCLC cell lines. eIF4E levels were significantly reduced in a dose-dependent manner in NSCLC cells treated with eIF4E-specific ASO (4EASO) compared with control ASO. Treatment of NSCLC cells with the 4EASO resulted in decreased cap-dependent complex formation, decreased cell proliferation and increased sensitivity to gemcitabine. At the molecular level, repression of eIF4E with ASO resulted in decreased expression of the oncogenic proteins VEGF, c-Myc and osteopontin, whereas expression of β-actin was unaffected. Based on these findings, we conclude that eIF4E-silencing therapy alone or in conjunction with chemotherapy represents a promising approach deserving of further investigation in future NSCLC clinical trials.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 13/1
/ 13/106
/ 13/109
/ 13/2
/ 38/1
/ 42/109
/ 692/308
/ 82/1
/ 82/80
/ 96
/ 96/2
/ Actin
/ Biomedical and Life Sciences
/ Carcinoma, Non-Small-Cell Lung - drug therapy
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Cell Proliferation - drug effects
/ Cell Proliferation - genetics
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - pharmacology
/ Dose-Response Relationship, Drug
/ Eukaryotic Initiation Factor-4E - genetics
/ Eukaryotic Initiation Factor-4E - metabolism
/ Humans
/ Lung Neoplasms - drug therapy
/ Molecular Targeted Therapy - methods
/ Non-small cell lung carcinoma
/ Oligonucleotides, Antisense - genetics
/ Oligonucleotides, Antisense - pharmacology
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