Presentation is loading. Please wait.

Presentation is loading. Please wait.

Sequence-dependent enhancement of paclitaxel toxicity in non–small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin  Dao M. Nguyen, MD, FRCSC,

Published byGodwin Holmes Modified over 5 years ago

Similar presentations

Presentation on theme: "Sequence-dependent enhancement of paclitaxel toxicity in non–small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin  Dao M. Nguyen, MD, FRCSC,"— Presentation transcript:

1 Sequence-dependent enhancement of paclitaxel toxicity in non–small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin  Dao M. Nguyen, MD, FRCSC, Aaron Chen, MS, Arnold Mixon, BS, David S. Schrump, MD, FACS  The Journal of Thoracic and Cardiovascular Surgery  Volume 118, Issue 5, Pages (November 1999) DOI: /S (99) Copyright © 1999 Mosby, Inc. Terms and Conditions

2 Fig. 1 Constitutive expression of p185 oncoprotein and its depletion by 17-AAGA in NSCLC cells. Normal human bronchial epithelial cells (NHBE) as well as H460 and H1299 cells express low levels of p185. Other cell lines overexpress this oncoprotein (15- to 31-fold higher than level detected in normal human bronchial epithelial cells). Exposure to either 20 nmol/L or 80 nmol/L 17-AAGA for 24 hours resulted in dose-dependent reduction of p185 in all cell lines tested. Data are mean ± SD for 3 independent experiments. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

3 Fig. 2 Dose-dependent growth inhibition of NSCLC in vitro by 17-AAGA. Cells were seeded in 96-well flat-bottom microtiter plates and, after overnight incubation, continuously exposed to varying doses of 17-AAGA for 96 hours. Viable cells were quantitated by MTT assay. IC50 values, estimated from dose-response curves, are indicated in parentheses. Data are mean ± SD for 3 independent experiments. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

4 Fig. 3 A, Representative dose-response curves of H661 (high p185) and H1299 (low p185) cells treated with paclitaxel (Taxol) alone or concurrently with either 20 nmol/L or 40 nmol/L 17-AAGA (schedule A combination). Data are mean ± SD for 4 independent experiments. B, Reduction of paclitaxel (Taxol) IC50 values by 17-AAGA in NSCLC cells expressing high levels of p185 (P = .001, P < .0001, P < .0001, P < for H358, H322, H661, and H522 cells, respectively, by 1-way analysis of variance). Data are mean ± SD for 4 independent experiments. Right upper corner graph indicates multiplicity of reduction of paclitaxel IC50 values (indicating enhanced paclitaxel sensitivity) in cells treated with paclitaxel and either 20 nmol/L or 40 nmol/L 17-AAGA. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

5 Fig. 4 A, Representative dose-response curves of H661 (high p185) and H1299 (low p185) cells treated with paclitaxel (Taxol, Tx) or schedule B drug combination. Exposure of cells to 17-AAGA for 24 hours before paclitaxel and 17-AAGA treatment induced paclitaxel resistance, as indicated by higher fractions of viable cells and translated into elevation of paclitaxel IC50 values. Data are mean ± SD for 4 independent experiments. B, Significant elevation of paclitaxel IC50 values (indicating decreased paclitaxel sensitivity) by schedule B drug combination in 5 cell lines studied (2 low p185 and 3 high p185 cell lines). The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

6 Fig. 5 Time-course of induction of cell cycle arrest at G1 phase by 17-AAGA treatment in H1299, H661, and H358 (P = .42 and P < [asterisk], P = .01 and P = .03 [number sign], and P = .19 and P = [double asterisk] for 17-AAGA treatment versus control at 24 hours and 48 hours, respectively, by the Student t test). Data are mean ± SD for 3 independent experiments. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

7 Fig. 6 Significant induction of apoptosis in H322 and H661 cells treated for 60 hours with schedule A combination (paclitaxel [Taxol] at 50 nmol/L and 500 nmol/L and 17-AAGA at 40 nmol/L). Control preparations were cells treated either with 17-AAGA or with paclitaxel (P = [asterisk], P = [number sign], P = .001 [double asterisk], and P = [double number sign] for schedule A combination versus paclitaxel alone by Student t test. Data are mean ± SD for 3 independent experiments. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

Download ppt "Sequence-dependent enhancement of paclitaxel toxicity in non–small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin  Dao M. Nguyen, MD, FRCSC,"

Similar presentations

The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural.

The selective epidermal growth factor receptor tyrosine kinase inhibitor PD suppresses expression of prometastasis phenotypes in malignant pleural.
Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: Activation of the mitochondria-dependent death-signaling.

Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: Activation of the mitochondria-dependent death-signaling.
Antiproliferative and apoptotic effects of rofecoxib on esophageal cancer in vitro1  Linda Vona-Davis, Ph.D., Dale R Riggs, Barbara J Jackson, David W.

Antiproliferative and apoptotic effects of rofecoxib on esophageal cancer in vitro1  Linda Vona-Davis, Ph.D., Dale R Riggs, Barbara J Jackson, David W.
Manish R. Patel, DO, Blake A

Manish R. Patel, DO, Blake A
Protective Function of p27KIP1 against Apoptosis in Small Cell Lung Cancer Cells in Unfavorable Microenvironments  Akira Masuda, Hirotaka Osada, Yasushi.

Protective Function of p27KIP1 against Apoptosis in Small Cell Lung Cancer Cells in Unfavorable Microenvironments  Akira Masuda, Hirotaka Osada, Yasushi.
Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3 Cell Physiol Biochem 2016;40:1221-1229.

Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3 Cell Physiol Biochem 2016;40:
Vascular endothelial growth factor expression in non-small-cell lung cancer: Prognostic significance in squamous cell carcinoma  Hideyuki Imoto, MD, Toshihiro.

Vascular endothelial growth factor expression in non-small-cell lung cancer: Prognostic significance in squamous cell carcinoma  Hideyuki Imoto, MD, Toshihiro.
Induction of apoptosis of lung and esophageal cancer cells treated with the combination of histone deacetylase inhibitor (trichostatin A) and protein.

Induction of apoptosis of lung and esophageal cancer cells treated with the combination of histone deacetylase inhibitor (trichostatin A) and protein.
Therapy-Resistant Cancer Stem Cells Have Differing Sensitivity to Photon versus Proton Beam Radiation  Xiaochun Zhang, MD, Steven H. Lin, MD, PhD, Bingliang.

Therapy-Resistant Cancer Stem Cells Have Differing Sensitivity to Photon versus Proton Beam Radiation  Xiaochun Zhang, MD, Steven H. Lin, MD, PhD, Bingliang.
Lost in translation The Journal of Thoracic and Cardiovascular Surgery

Lost in translation The Journal of Thoracic and Cardiovascular Surgery
The Autophagy Inhibitor Chloroquine Overcomes the Innate Resistance of Wild-Type EGFR Non-Small-Cell Lung Cancer Cells to Erlotinib  Yiyu Zou, PhD, Yi-He.

The Autophagy Inhibitor Chloroquine Overcomes the Innate Resistance of Wild-Type EGFR Non-Small-Cell Lung Cancer Cells to Erlotinib  Yiyu Zou, PhD, Yi-He.
Inactivation of Both FHIT and p53 Cooperate in Deregulating Proliferation-Related Pathways in Lung Cancer  Francesca Andriani, PharmD, Elena Roz, MD,

Inactivation of Both FHIT and p53 Cooperate in Deregulating Proliferation-Related Pathways in Lung Cancer  Francesca Andriani, PharmD, Elena Roz, MD,
Manish R. Patel, DO, Blake A

Manish R. Patel, DO, Blake A
Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis  Dao M Nguyen, MD, Dominique.

Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis  Dao M Nguyen, MD, Dominique.
Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor–related apoptosis-inducing.

Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor–related apoptosis-inducing.
Therapy-Resistant Cancer Stem Cells Have Differing Sensitivity to Photon versus Proton Beam Radiation  Xiaochun Zhang, MD, Steven H. Lin, MD, PhD, Bingliang.

Therapy-Resistant Cancer Stem Cells Have Differing Sensitivity to Photon versus Proton Beam Radiation  Xiaochun Zhang, MD, Steven H. Lin, MD, PhD, Bingliang.
Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma  Mor-Li Hartman, PhD, John Matthew Esposito, BA, Beow Yong.

Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma  Mor-Li Hartman, PhD, John Matthew Esposito, BA, Beow Yong.
A High Content Clonogenic Survival Drug Screen Identifies MEK Inhibitors as Potent Radiation Sensitizers for KRAS Mutant Non–Small-Cell Lung Cancer  Steven.

A High Content Clonogenic Survival Drug Screen Identifies MEK Inhibitors as Potent Radiation Sensitizers for KRAS Mutant Non–Small-Cell Lung Cancer  Steven.
Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer  Peng Kuang, Zuhua.

Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer  Peng Kuang, Zuhua.
Depletion of DNA methyltransferase 1 and/or DNA methyltransferase 3b mediates growth arrest and apoptosis in lung and esophageal cancer and malignant.

Depletion of DNA methyltransferase 1 and/or DNA methyltransferase 3b mediates growth arrest and apoptosis in lung and esophageal cancer and malignant.

Similar presentations

Ads by Google