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result sql = Small interfering RNA targeting 14-3-3ζ increases efficacy of chemotherapeutic agents in head and neck cancer cells.
Small interfering RNA targeting 14-3-3ζ increases efficacy of chemotherapeutic agents in head and neck cancer cells.
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char = v;code = 118
char = i;code = 105
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char = ;code = 32
char = c;code = 99
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result sql = Patients diagnosed in advanced stages of head and neck squamous cell carcinoma often show limited response to chemotherapeutic agents. Recently, we reported the overexpression of 14-3-3ζ protein in head and neck premalignant and cancer tissues using liquid chromatography-tandem mass spectrometry with isotopic labeling and revealed its significance as a prognostic marker using immunohistochemical analysis. In this study, we determined the potential of 14-3-3ζ as a therapeutic target for head and neck cancer. Small interfering RNA (siRNA) targeting 14-3-3ζ was used to downregulate its expression in head and neck cancer cells in culture. Cell cycle analysis showed that head and neck cancer cells transfected with siRNA targeting 14-3-3ζ showed G(2)-M arrest. THESE SIRNA TRANSFECTANTS ALSO SHOWED INCREASED CELL DEATH ON TREATMENT WITH ANY ONE OF THE FOLLOWING CHEMOTHERAPEUTIC AGENTS: cisplatin, 5-fluorouracil, paclitaxel, or doxorubicin in comparison with the no transfection controls. Flow cytometric analysis using propidium iodide staining showed increased sub-G(0) fraction in siRNA-transfected cells treated with any of these chemotherapeutic agents, suggesting cell death; in addition, Annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay revealed increased apoptosis. Taken together, our results strongly showed that downregulation of 14-3-3ζ expression may serve to improve the sensitivity of head and neck cancer cells to chemotherapeutic agents.

Publication: Mol. Cancer Ther. 2010 Oct ;9(10)::2676-88. :doi: 10.1158/1535-7163.MCT-10-0312.
Publication Date: 2010 Oct
Study Author(s): Matta, Ajay;DeSouza, Leroi V;Ralhan, Ranju;Siu, K W Michael;
Institution: Department of Chemistry and Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada.
Shortcut link to this study:
Patients diagnosed in advanced stages of head and neck squamous cell carcinoma often show limited response to chemotherapeutic agents. Recently, we reported the overexpression of 14-3-3ζ protein in head and neck premalignant and cancer tissues using liquid chromatography-tandem mass spectrometry with isotopic labeling and revealed its significance as a prognostic marker using immunohistochemical analysis. In this study, we determined the potential of 14-3-3ζ as a therapeutic target for head and neck cancer. Small interfering RNA (siRNA) targeting 14-3-3ζ was used to downregulate its expression in head and neck cancer cells in culture. Cell cycle analysis showed that head and neck cancer cells transfected with siRNA targeting 14-3-3ζ showed G(2)-M arrest. THESE SIRNA TRANSFECTANTS ALSO SHOWED INCREASED CELL DEATH ON TREATMENT WITH ANY ONE OF THE FOLLOWING CHEMOTHERAPEUTIC AGENTS: cisplatin, 5-fluorouracil, paclitaxel, or doxorubicin in comparison with the no transfection controls. Flow cytometric analysis using propidium iodide staining showed increased sub-G(0) fraction in siRNA-transfected cells treated with any of these chemotherapeutic agents, suggesting cell death; in addition, Annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay revealed increased apoptosis. Taken together, our results strongly showed that downregulation of 14-3-3ζ expression may serve to improve the sensitivity of head and neck cancer cells to chemotherapeutic agents.
PMID: 20924126

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