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Results: 5

1.
Fig. 5

Fig. 5. From: Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.

Comparative antitumor activity of combination ganetespib plus docetaxel treatment in NSCLC xenograft models. Summary of antitumor efficacy of ganetespib and docetaxel either alone or in combination in 6 NSCLC xenograft models.%T/C values are reported. Ganetespib was dosed at 50 mg/kg except for HCC827 (75 mg/kg) and H1975 (100 mg/kg). Docetaxel was dosed at 4 mg/kg except for H1975 (5 mg/kg)

David A. Proia, et al. Invest New Drugs. 2012 December;30(6):2201-2209.
2.
Fig. 3

Fig. 3. From: Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.

In vivo activity of ganetespib in combination with paclitaxel or docetaxel in H1975 xenografts. a Human NSCLC H1975 tumor-bearing SCID mice were i.v. dosed with ganetespib (50 mg/kg) and paclitaxel (7.5 mg/kg) alone or in combination on a 1X/week schedule for 3 weeks. Data represent the mean and S.E.M. The combination of ganetespib and paclitaxel displayed significantly greater efficacy than either agent alone (*, p < 0.05). b Human NSCLC H1975 tumor-bearing SCID mice were i.v. dosed with ganetespib (100 mg/kg) and docetaxel (5 mg/kg) alone or in combination on a 1X/week schedule for 3 weeks. Data represent mean and S.E.M. The combination of ganetespib and docetaxel resulted in tumor regression (24%)

David A. Proia, et al. Invest New Drugs. 2012 December;30(6):2201-2209.
3.
Fig. 2

Fig. 2. From: Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.

Median effect analysis of the combinatorial activity of ganetespib with paclitaxel, docetaxel and vincristine in H1975 cells in vitro. Drugs were added to H1975 cells at fixed, non-constant concentration ratios for 72 h and viability assessed by Alamar blue assay. Each point represents a CI value for a specific combination of drug concentrations. Data points below the line in the isobologram represent synergy, whereas data points above indicate antagonism between the drug pairs. a Isobologram analysis of ganetespib in combination with paclitaxel. b Isobologram analysis of ganetespib in combination with docetaxel. c Isobologram analysis of ganetespib in combination with vincristine

David A. Proia, et al. Invest New Drugs. 2012 December;30(6):2201-2209.
4.
Fig. 1

Fig. 1. From: Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.

Single agent effects on cell viability, Hsp90 client protein degradation and cell cycle distribution in H1975 NSCLC cells. a H1975 cells were treated with ganetespib, paclitaxel, docetaxel or vincristine over a broad dose range (0.1 to 330 nM) for 72 h and cell viability assessed by alamarBlue staining. b Temporal and dose-dependent effects on Hsp90 client proteins by ganetespib. H1975 cells were treated with increasing concentrations of ganetespib for 4 and 24 h and cell lysates subject to immunoblotting using the indicated antibodies. c H1975 cells were treated with the indicated doses of docetaxel or ganetespib and cell cycle distribution determined by flow cytometry 24 h post-treatment

David A. Proia, et al. Invest New Drugs. 2012 December;30(6):2201-2209.
5.
Fig. 4

Fig. 4. From: Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.

Combination of ganetespib and docetaxel induces enhanced antitumor efficacy and apoptosis in NSCLC xenografts. a SCID mice bearing HCC827 NSCLC xenografts were i.v. dosed with ganetespib (75 mg/kg) and docetaxel (4 mg/kg) alone or in combination on a 1X/week schedule for 4 weeks. Data represent the mean and S.E.M. b SCID mice bearing H1437 xenografts were i.v. dosed with ganetespib (50 mg/kg) and docetaxel (4 mg/kg) alone or in combination on a 1X/week schedule for 4 weeks. Data represent the mean and S.E.M. The combination of ganetespib and docetaxel displayed significantly greater efficacy than either agent alone (*, p < 0.05). c H1437 tumor-bearing SCID mice were treated with a single dose of vehicle, ganetespib (50 mg/kg), docetaxel (4 mg/kg) or ganetespib plus docetaxel and tumors harvested 24 h later. Immunohistochemical staining for TUNEL positivity (apoptosis) of tumor cross sections from vehicle control, ganetespib, docetaxel, or ganetespib + docetaxel treated animals. Original magnification, 40X. d Quantitation of TUNEL-positive areas of tumors as described in (C). Data represent the mean and S.D. (*, p < 0.05; one-way ANOVA)

David A. Proia, et al. Invest New Drugs. 2012 December;30(6):2201-2209.

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