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21 février 2012 2 21 /02 /février /2012 13:03

J Control Release. 2011 Dec 30. [Epub ahead of print]

 

Combination radiofrequency (RF) ablation and IV liposomal heat shock protein suppression: Reduced tumor growth and increased animal endpoint survival in a small animal tumor model.

 

Yang W, Ahmed M, Tasawwar B, Levchenko T, Sawant RR, Torchilin V, Goldberg SN.

 

Source

 

Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, United States; Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.

 

Abstract

 

BACKGROUND:

 

To investigate the effect of IV liposomal quercetin (a known down-regulator of heat shock proteins) alone and with liposomal doxorubicin on tumor growth and end-point survival when combined with radiofrequency (RF) tumor ablation in a rat tumor model.

 

METHODS:

 

Solitary subcutaneous R3230 mammary adenocarcinoma tumors (1.3-1.5cm) were implanted in 48 female Fischer rats. 

Initially, 32 tumors (n=8, each group) were randomized into four experimental groups: 

  1. conventional monopolar RF alone (70°C for 5min), 
  2. IV liposomal quercetin alone (1mg/kg), 
  3. IV liposomal quercetin followed 24hr later with RF, and 
  4. no treatment. 

 

Next, 16 additional tumors were randomized into two groups (n=8, each) that received a combined RF and liposomal doxorubicin (15min post-RF, 8mg/kg) either with or without liposomal quercetin. 

Kaplan-Meier survival analysis was performed using a tumor diameter of 3.0cm as the defined survival endpoint.

 

RESULTS:

 

Differences in endpoint survival and tumor doubling time among the groups were highly significant (P<0.001). Endpoint survivals were 12.5±2.2days for the control group, 16.6±2.9days for tumors treated with RF alone, 15.5±2.1days for tumors treated with liposomal quercetin alone, and 22.0±3.9days with combined RF and quercetin. Additionally, combination quercetin/RF/doxorubicin therapy resulted in the longest survival (48.3±20.4days), followed by RF/doxorubicin (29.9±3.8days).

 

CONCLUSIONS:

 

IV liposomal quercetin in combination with RF ablation reduces tumor growth rates and improves animal endpoint survival. Further increases in endpoint survival can be seen by adding an additional anti-tumor adjuvant agent liposomal doxorubicin. This suggests that targeting several post-ablation processes with multi-drug nanotherapies can increase overall ablation efficacy.

 

Copyright © 2011 Elsevier B.V. All rights reserved.

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