scholarly journals Extracellular Heat Shock Protein 90 Signals through Subdomain II and the NPVY Motif of LRP-1 Receptor to Akt1 and Akt2: a Circuit Essential for Promoting Skin Cell Migration In Vitro and Wound Healing In Vivo

2013 ◽  
Vol 33 (24) ◽  
pp. 4947-4959 ◽  
Author(s):  
F. Tsen ◽  
A. Bhatia ◽  
K. O'Brien ◽  
C.-F. Cheng ◽  
M. Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Skin Cell

scholarly journals A Brain Penetrating Heat-Shock Protein 90 Inhibitor NXD30001 Inhibits Glioblastoma as a Monotherapy or in Combination With Radiation

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Hao Chen ◽  
Jialiang Wang ◽  
Hengli Tian
Keyword(s):  
Stem Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Median Survival ◽  
Therapeutic Potential ◽  
Heat Shock Protein 90 ◽  
Tumor Bearing ◽  
Client Proteins

Abstract INTRODUCTION It has been increasingly recognized that glioblastoma multiforme (GBM) is a highly heterogeneous disease, which is initiated and sustained by molecular alterations in an array of signal transduction pathways. Heat-shock protein 90 (Hsp90) is a molecular chaperone to be critically implicated in folding and activation of a diverse group of client proteins, many of which are key regulators of important glioblastoma biology. METHODS To determine the therapeutic potential of targeting Hsp90 in glioblastoma, we assessed the anti-neoplastic efficacy of NXD30001, a brain-penetrating Hsp90 inhibitor as a monotherapy or in combination with radiation, both in Vitro and in Vivo. RESULTS Our results demonstrated that NXD30001 potently inhibited neurosphere formation, growth and survival of CD133 + glioblastoma stem cells (GSCs) with the half maximal inhibitory concentrations (IC50) at low nanomolar concentrations. At suboptimal concentrations, inhibition of Hsp90 did not exert cytotoxic activity but rather increased radiosensitivity in GSCs. CD133- GBM cells were less sensitive and not radiosensitized by NXD30001. In lines with its cytotoxic and radiosensitizing effects, NXD30001 dose-dependently decreased phosphorylation protein levels of multiple Hsp90 client proteins, including those playing key roles in GSCs, such as EGFR, Akt, c-Myc, and Notch1. In addition, combining NXD30001 with radiation could impair DNA damage response and ER stress response to induce apoptosis of GSCs. Treatment of orthotopic glioblastoma tumors with NXD30001 extended median survival of tumor-bearing mice by approximately 20% (treated 37 days vs vehicle 31 d, P = .0026). Radiation alone increased median survival of tumor-bearing mice from 31 to 38 d, combination with NXD30001 further extended survival to 43 d (P = .0089). CONCLUSION Our results suggest that GBM stem cells (CD133+) are more sensitive to NXD30001 than non-stem GBM cells (CD133-). Furthermore, combination NXD30001 with radiation significantly inhibits GBM progression than use it as a monotherapy by targeting GSCs.

scholarly journals A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: In vitro and In vivo Study

2008 ◽  
Vol 68 (15) ◽  
pp. 6260-6270 ◽  
Author(s):  
Ana Sofia Martins ◽  
José Luis Ordoñez ◽  
Alfredo García-Sánchez ◽  
David Herrero ◽  
Victoria Sevillano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Ewing Sarcoma ◽  
Heat Shock Protein 90 ◽  
Pivotal Role ◽  
In Vivo Study ◽  
Insulin Like Growth Factor

Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues

2007 ◽  
Vol 6 (4) ◽  
pp. 1198-1211 ◽  
Author(s):  
Swee Y. Sharp ◽  
Chrisostomos Prodromou ◽  
Kathy Boxall ◽  
Marissa V. Powers ◽  
Joanna L. Holmes ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperone ◽  
Heat Shock Protein 90

Abstract: P678 HEAT SHOCK PROTEIN 90 (HSP90) INHIBITORS ATTENUATE INFLAMATORY RESPONSES IN VITRO AND IN VIVO

2009 ◽  
Vol 10 (2) ◽  
pp. e864
Author(s):  
J Madrigal-Matute ◽  
ó López-Franco ◽  
L Blanco-Colio ◽  
B Muñoz-Garcia ◽  
P Ramos-Mozo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitors
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