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Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma  Mor-Li Hartman, PhD, John Matthew Esposito, BA, Beow Yong.

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Presentation on theme: "Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma  Mor-Li Hartman, PhD, John Matthew Esposito, BA, Beow Yong."— Presentation transcript:

1 Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma 
Mor-Li Hartman, PhD, John Matthew Esposito, BA, Beow Yong Yeap, ScD, David John Sugarbaker, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 139, Issue 5, Pages (May 2010) DOI: /j.jtcvs Copyright © Terms and Conditions

2 Figure 1 Cisplatin dose-response curves in malignant pleural mesothelioma cell lines. Effect of loss of cell viability detected with different doses of cisplatin (1–500-μmol/L) in 6 malignant pleural mesothelioma cell lines. Results represent mean of at least 3 experiments; bars represent SD. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

3 Figure 2 Sirolimus dose-response curves in malignant pleural mesothelioma cell lines. Effect of loss of cell viability detected with different doses of sirolimus (1–500 nmol/L) and time courses in 6 malignant pleural mesothelioma cell lines. Results represent mean of at least 3 experiments; bars represent SD. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

4 Figure 3 Sirolimus and cisplatin combination in malignant pleural mesothelioma cell lines. A, Effects of loss of cell viability in different malignant pleural mesothelioma cell lines (MS589, MS428, JMN1B, and MS924) with sirolimus (RAP), cisplatin (CIS), combination of both drugs (RAP + CIS), and nontreatment control (CT) of dimethyl sulfoxide vehicle. For each cell line, enlarged figure near each graph shows increased loss of cell viability from both drugs versus cisplatin alone at specific time points. Columns represent mean of 4 wells; bars represent SD. Each P value is presented in box. B, Malignant pleural mesothelioma cell lines MS428, MS924, and H2052 were treated as in part A and photographed 24 hours after drugs were washed out. Original magnification 200×; abbreviations as in part A. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

5 Figure 4 Dephosphorylation of Akt, p70 S6 kinase, and 4E-BP1 after sirolimus and cisplatin combined treatment. Western blot analysis demonstrates phosphorylation status of the Akt/mTOR pathway proteins using specific antibodies (Phospho) against specific phosphorylation sites (I-IV) of the indicated proteins. Column A represents malignant pleural mesothelioma cell line MS428. Column B represents malignant pleural mesothelioma cell line H2052. Both cell lines were treated with sirolimus (R), cisplatin (C), and the combination of both drugs (R + C). Untreated cells in vehicle (dimethyl sulfoxide) were used as control (CT). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions


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