title: Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model.
abstract: OBJECTIVE
  The purpose of this study was to explore the effects of MIH and radiotherapy alone or combined on metastatic breast cancer and the underlying mechanisms.
  
  
  METHODS
  A murine 4T1 metastatic breast cancer model was established and randomly assigned into four treatment groups: C (control), R (radiotherapy), MIH, and MIH+R. Tumour volume, lung metastasis, the expression of Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were evaluated.
  
  
  RESULTS
  Group MIH + R showed significantly reduced tumour volume, lung metastasis, improved survival and increased Bax expression compared to group R or MIH (P<0.05). MMP-9 expression in the primary tumour tissue was significantly increased in group R compared to the other groups (P<0.05), which could be brought down by combined MIH treatment. Group MIH +R showed significantly higher CD4(+) T cell percentage as well as CD4(+)/CD8(+) cell ratio than group R (P<0.05). Group MIH+R showed significantly higher serum levels of TNF-α, IFN-γ and IL-2 than group R (P<0.05).
  
  
  CONCLUSIONS
  MIH not only promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell death, but also improves cellular immunity in mice under radiotherapy and decreases the potential of radiotherapy to enhance MMP-9 expression, which leads to significant improvement in lung metastasis and overall survival of mice under combined treatment of MIH and R. This study is the first to have explored the effect of combined hyperthermia and radiotherapy on tumour metastasis and the underlying mechanisms. It provides insights into the application of MIH as an adjuvant to radiotherapy for metastatic breast cancer.
authors.affiliation: Department of Radiation Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Xuping
authors.initials: X
authors.lastname: Xi
authors.forename: Bingqiang
authors.initials: B
authors.lastname: Hu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhao
authors.forename: Yuping
authors.initials: Y
authors.lastname: Liao
authors.forename: Jintian
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D005260:Female; D006979:Hyperthermia, Induced / Q000379:methods*; D007111:Immunity, Cellular; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008280:Magnetics; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000528:radiation effects; D051028:bcl-2-Associated X Protein
chemical_list: D016207:Cytokines; D051028:bcl-2-Associated X Protein; D020780:Matrix Metalloproteinase 9