PMID- 20160000
OWN - NLM
STAT- MEDLINE
DCOM- 20100506
LR  - 20211020
IS  - 1527-1315 (Electronic)
IS  - 0033-8419 (Print)
IS  - 0033-8419 (Linking)
VI  - 255
IP  - 1
DP  - 2010 Apr
TI  - Liposomal doxorubicin increases radiofrequency ablation-induced tumor destruction 
      by increasing cellular oxidative and nitrative stress and accelerating apoptotic 
      pathways.
PG  - 62-74
LID - 10.1148/radiol.09091196 [doi]
AB  - PURPOSE: To determine if oxidative and nitrative stress and/or apoptosis 
      contribute to increased coagulation when combining radiofrequency (RF) ablation 
      with liposomal doxorubicin. MATERIALS AND METHODS: Animal care committee approval 
      was obtained. R3230 mammary adenocarcinomas in Fischer rats were treated with 
      either RF ablation (n = 43), 1 mg of intravenously injected liposomal doxorubicin 
      (n = 26), or combined therapy (n = 30) and were compared with control subjects (n 
      = 11). A subset of animals receiving combination therapy (n = 24) were treated in 
      the presence or absence of N-acetylcysteine (NAC) administered 24 hours and 1 
      hour before RF ablation. Tumors were analyzed 2 minutes to 72 hours after 
      treatment to determine the temporal range of response by using 
      immunohistochemical staining of the apoptosis marker cleaved caspase-3, 
      phosphorylated gammaH2AX, and HSP70 and of markers of oxidative and nitrative 
      stress (8-hydroxydeoxyguanosine [8-OHdG], 4-hydroxynonenal [4-HNE]-modified 
      proteins, and nitrotyrosine [NT]). Statistical analyses, including t tests and 
      analysis of variance for comparisons where appropriate, were performed. RESULTS: 
      By 4 hours after RF ablation alone, a 0.48-mm +/- 0.13 (standard deviation) 
      peripheral band with 57.0% +/- 7.3 cleaved caspase-3 positive cells was noted at 
      the ablation margin, whereas a 0.73-mm +/- 0.18 band with 77.7% +/- 6.3 
      positivity was seen for combination therapy (P < .03 for both comparisons). 
      Combination therapy caused increased and earlier staining for 4-HNE-modified 
      proteins, 8-OHdG, NT, and gammaH2AX with colocalization to cleaved caspase-3 
      staining. A rim of increased HSP70 was identified peripheral to the area of 
      cleaved caspase-3. Parameters of oxidative and nitrative stress were 
      significantly inhibited by NAC 1 hour following RF ablation, resulting in 
      decreased cleaved caspase-3 positivity (0.28-mm +/- 0.09 band of 25.9% +/- 7.4 
      positivity vs 0.59-mm +/- 0.11 band of 62.9% +/- 6.0 positivity, P < .001 for 
      both comparisons). CONCLUSION: Combining RF ablation with liposomal doxorubicin 
      increases cell injury and apoptosis in the zone of increased coagulation by using 
      a mechanism that involves oxidative and nitrative stress that leads to 
      accelerated apoptosis.
CI  - RSNA, 2010
FAU - Solazzo, Stephanie A
AU  - Solazzo SA
AD  - Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth 
      Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, 
      Boston, MA 02215, USA.
FAU - Ahmed, Muneeb
AU  - Ahmed M
FAU - Schor-Bardach, Rachel
AU  - Schor-Bardach R
FAU - Yang, Wei
AU  - Yang W
FAU - Girnun, Geoffrey D
AU  - Girnun GD
FAU - Rahmanuddin, Syed
AU  - Rahmanuddin S
FAU - Levchenko, Tatyana
AU  - Levchenko T
FAU - Signoretti, Sabina
AU  - Signoretti S
FAU - Spitz, Douglas R
AU  - Spitz DR
FAU - Torchilin, Vladimir
AU  - Torchilin V
FAU - Goldberg, S Nahum
AU  - Goldberg SN
LA  - eng
GR  - R01 CA100045/CA/NCI NIH HHS/United States
GR  - R01 CA133114/CA/NCI NIH HHS/United States
GR  - R01 HL055519/HL/NHLBI NIH HHS/United States
GR  - 2R01 HL55519/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100216
PL  - United States
TA  - Radiology
JT  - Radiology
JID - 0401260
RN  - 0 (Aldehydes)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Histones)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 80168379AG (Doxorubicin)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - EC 3.4.22.- (Caspase 3)
RN  - G9481N71RO (Deoxyguanosine)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
CIN - Radiology. 2010 Apr;255(1):1-2. PMID: 20308435
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Acetylcysteine/pharmacology
MH  - Aldehydes/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - *Catheter Ablation
MH  - Combined Modality Therapy
MH  - DNA Damage
MH  - Deoxyguanosine/analogs & derivatives/metabolism
MH  - Doxorubicin/*pharmacology
MH  - Female
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Histones/metabolism
MH  - Immunoenzyme Techniques
MH  - Mammary Neoplasms, Experimental/*drug therapy/metabolism/*surgery
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Inbred F344
MH  - Tyrosine/analogs & derivatives/metabolism
PMC - PMC2843831
EDAT- 2010/02/18 06:00
MHDA- 2010/05/07 06:00
PMCR- 2011/04/01
CRDT- 2010/02/18 06:00
PHST- 2010/02/18 06:00 [entrez]
PHST- 2010/02/18 06:00 [pubmed]
PHST- 2010/05/07 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - radiol.09091196 [pii]
AID - 09091196 [pii]
AID - 10.1148/radiol.09091196 [doi]
PST - ppublish
SO  - Radiology. 2010 Apr;255(1):62-74. doi: 10.1148/radiol.09091196. Epub 2010 Feb 16.