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Induction of apoptosis in malignant pleural mesothelioma cells by activation of the Fas (Apo-1/CD95) death-signal pathway  John H. Stewart, MD, Dao M.

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Presentation on theme: "Induction of apoptosis in malignant pleural mesothelioma cells by activation of the Fas (Apo-1/CD95) death-signal pathway  John H. Stewart, MD, Dao M."— Presentation transcript:

1 Induction of apoptosis in malignant pleural mesothelioma cells by activation of the Fas (Apo-1/CD95) death-signal pathway  John H. Stewart, MD, Dao M. Nguyen, MD, G.Aaron Chen, MS, David S. Schrump, MD, Sponsor: Valerie Rusch, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 123, Issue 2, Pages (February 2002) DOI: /mtc Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

2 Fig. 1 Flow cytometric analysis of Fas expression in mesothelioma and control cells. Jurkat cells, which express high levels of Fas, were used as positive controls for subsequent experiments. These data are representative of 3 independent experiments that yielded similar results. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /mtc ) Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

3 Fig. 2 Upregulation of Fas expression in H2595 (A) and REN (B) MPM cell lines after 24 hours' exposure to either LAK cells or cell-free LAK supernatant. Incubation of these lines with fresh basal LAK medium without (control) or with interferon γ (100 IU/mL) did not alter the basal expression of Fas. These data are representative of 3 independent experiments that yielded similar results. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /mtc ) Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

4 Fig. 3 Western blot analysis of caspases 3, 8, and 9 in human umbilical vein endothelial cells HUVECs ) and MPM cells. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /mtc ) Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

5 Fig. 4 Induction of apoptosis in Jurkat lymphoma, H28, and H2373 mesothelioma cells and NHBE cells after exposure to sFasL. These sFasL-sensitive tumor cells underwent significant apoptosis after treatment with 50 ng/ml sFasL. No apoptosis was detected in NHBE cells under similar conditions. These data are means ± SD of 3 independent experiments. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /mtc ) Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

6 Fig. 5 Induction of apoptosis in H2052 (A) and H513 (B) MPM cells after exposure to normal medium, sFasL alone (50 ng.mL for 24 hours), CDDP (3 μg/mL for 24 hours) alone, or CDDP-sFasL. These data are representative of 3 independent experiments that yielded similar results. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /mtc ) Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

7 Fig. 6 In vivo response of H2373 MPM xenograft to locoregional delivery of sFasL: A, tumor burden 6 weeks after injection of H2373 MPM cells; B, tumor burden 1 week after injection of H2373 MPM cells; C, inhibition of tumor growth after treatment with sFasL commencing 1 week after tumor implantation; D, tumor burden 2 weeks after implantation of H2373 MPM cells, E, response to sFasL injections starting 2 week after tumor implantation. A similar magnitude of response was observed in all animals within each group. Representative digital photographs are shown here. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /mtc ) Copyright © 2002 American Association for Thoracic Surgery Terms and Conditions

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