| Title | Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model |
| Authors | Yang, Wei Ahmed, Muneeb Tasawwar, Beenish Levchenko, Tatyana Sawant, Rupa R. Collins, Michael Signoretti, Sabina Torchilin, Vladimir Goldberg, S. Nahum |
| Affiliation | Harvard Univ, Beth Israel Deaconess Med Ctr, Minimally Invas Tumor Therapies Lab, Dept Radiol,Med Sch, Boston, MA 02215 USA. Peking Univ Canc Hosp & Inst, Minist Educ, Dept Ultrasound, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Sch Med, Boston, MA 02215 USA. Hadassah Hebrew Univ Med Ctr, Dept Radiol, Div Image Guided Therapy, Jerusalem, Israel. Harvard Univ, Beth Israel Deaconess Med Ctr, Minimally Invas Tumor Therapies Lab, Dept Radiol,Med Sch, WCC 308-B,1 Deaconess Rd, Boston, MA 02215 USA. |
| Keywords | apoptosis heat shock protein liposomal quercetin liposomal doxorubicin radiofrequency tumour ablation HEPATOCELLULAR-CARCINOMA THERMAL ABLATION ANTITUMOR IMMUNITY DENDRITIC CELLS IN-VIVO DOXORUBICIN COAGULATION EXPRESSION HEAT-SHOCK-PROTEIN-70 ACCUMULATION |
| Issue Date | 2011 |
| Publisher | 国际高温杂志 |
| Citation | INTERNATIONAL JOURNAL OF HYPERTHERMIA.2011,27,(6),527-538. |
| Abstract | Purpose: To investigate the effect of heat shock protein (HSP) modulation on tumour coagulation by combining radiofrequency (RF) ablation with adjuvant liposomal quercetin and/or doxorubicin in a rat tumour model. Methods: Sixty R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved study. Initially, 60 tumours (n=6, each subgroup) were randomised into five groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1 mg/kg), (3) IV liposomal quercetin followed 24 h later with RF, (4) RF followed 15 min later by IV liposomal doxorubicin (8 mg/kg), (5) IV liposomal quercetin 24 h before RF followed by IV liposomal doxorubicin 15 min post-ablation. Animals were sacrificed 4 or 24 h post-treatment and gross coagulation diameters were compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved caspase-3 expression. Comparisons were performed by using Student t-tests or ANOVA. Results: Combination RF-quercetin significantly increased coagulation size compared with either RF or liposomal quercetin alone (13.1 +/- 0.7mm vs. 8.8 +/- 1.2mm or 2.3 +/- 1.3 mm, respectively, P < 0.001 for all comparisons). Triple therapy (quercetin-RF-doxorubicin) showed larger coagulation diameter (14.5 +/- 1.0mm) at 24 h than quercetin-RF (P=0.016) or RF-doxorubicin (13.2 +/- 1.3 mm, P=0.042). Combination quercetin-RF decreased Hsp70 expression compared with RF alone at both 4 h (percentage of stained cells/hpf 22.4 +/- 13.9% vs. 38.8 +/- 16.1%, P < 0.03) and 24 h (45.2 +/- 10.5% vs. 81.1 +/- 3.6%, P < 0.001). Quercetin-RF increased cleaved caspase-3 expression at both 4 h (percentage of stained cells/hpf 50.7 +/- 13.4% vs. 41.9 +/- 15.1%, P < 0.03) and 24 h (37.4 +/- 7.8% vs. 33.2 +/- 6.5%, P=0.045); with, triple therapy (quercetin-RF- doxorubicin) resulting in the highest levels of apoptosis (45.1 +/- 10.7%) at 24 h. Similar trends were observed for rim thickness. Conclusions: Suppression of HSP production using adjuvant liposomal quercetin can increase apoptosis and improve RF ablation-induced tumour destruction. Further increases in tumour coagulation can be seen including an additional anti-tumour adjuvant agent such as liposomal doxorubicin. |
| URI | http://hdl.handle.net/20.500.11897/241155 |
| ISSN | 0265-6736 |
| DOI | 10.3109/02656736.2011.582474 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
