PMID- 22911830
OWN - NLM
STAT- MEDLINE
DCOM- 20130222
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor 
      specific immunity in a transplant tumor model of prostate cancer.
PG  - e41632
LID - 10.1371/journal.pone.0041632 [doi]
LID - e41632
AB  - OBJECTIVE: In this study, we explored the use of mechanical high intensity 
      focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection 
      of the primary tumor. We also investigated the role of signal transducer and 
      activator of transcription 3 (STAT3) in M-HIFU elicited anti-tumor immune 
      response using a transplant tumor model of prostate cancer. METHODS: RM-9, a 
      mouse prostate cancer cell line with constitutively activated STAT3, was 
      inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a 
      maximum tumor diameter of 5 approximately 6 mm) were treated by M-HIFU or sham exposure two 
      days before surgical resection of the primary tumor. Following recovery, if no 
      tumor recurrence was observed in 30 days, tumor rechallenge was performed. The 
      growth of the rechallenged tumor, survival rate and anti-tumor immune response of 
      the animal were evaluated. RESULTS: No tumor recurrence and distant metastasis 
      were observed in both treatment groups employing M-HIFU + surgery and surgery 
      alone. However, compared to surgery alone, M-HIFU combined with surgery were 
      found to significantly inhibit the growth of rechallenged tumors, down-regulate 
      intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor 
      draining lymph nodes (TDLNs), and improve the host survival. Furthermore, M-HIFU 
      combined with surgery was found to significantly decrease the level of 
      immunosuppression with concomitantly increased number and activities of dendritic 
      cells, compared to surgery alone. CONCLUSION: Our results demonstrate that M-HIFU 
      can inhibit STAT3 activities, and when combined synergistically with surgery, may 
      provide a novel and promising strategy for the treatment of prostate cancers.
FAU - Huang, Xiaoyi
AU  - Huang X
AD  - Department of Mechanical Engineering and Materials Science, Duke University, 
      Durham, North Carolina, United States of America.
FAU - Yuan, Fang
AU  - Yuan F
FAU - Liang, Meihua
AU  - Liang M
FAU - Lo, Hui-Wen
AU  - Lo HW
FAU - Shinohara, Mari L
AU  - Shinohara ML
FAU - Robertson, Cary
AU  - Robertson C
FAU - Zhong, Pei
AU  - Zhong P
LA  - eng
GR  - R21 CA135221/CA/NCI NIH HHS/United States
GR  - 5R21CA135221-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120724
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/immunology
MH  - Disease Models, Animal
MH  - *High-Intensity Focused Ultrasound Ablation
MH  - Humans
MH  - Immunity/*immunology
MH  - Lymph Nodes/immunology
MH  - Lymphocyte Count
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Transplantation
MH  - Phosphorylation
MH  - Prostatic Neoplasms/*immunology/*pathology/therapy
MH  - STAT3 Transcription Factor/*metabolism
MH  - Spleen/immunology
MH  - Survival Analysis
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - T-Lymphocytes, Regulatory/immunology
PMC - PMC3404041
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/23 06:00
MHDA- 2013/02/23 06:00
PMCR- 2012/07/24
CRDT- 2012/08/23 06:00
PHST- 2012/02/24 00:00 [received]
PHST- 2012/06/22 00:00 [accepted]
PHST- 2012/08/23 06:00 [entrez]
PHST- 2012/08/23 06:00 [pubmed]
PHST- 2013/02/23 06:00 [medline]
PHST- 2012/07/24 00:00 [pmc-release]
AID - PONE-D-12-05711 [pii]
AID - 10.1371/journal.pone.0041632 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e41632. doi: 10.1371/journal.pone.0041632. Epub 2012 Jul 24.