title: Inhibition of B16 murine melanoma metastasis and enhancement of immunity by fever-range whole body hyperthermia.
abstract: OBJECTIVE
  Whole body hyperthermia (WBH) has been regarded as a promising alternative therapy to cure late stage cancer with metastasis. As the final biological and therapeutic effects are dependent on the specific protocol, the potential of using a microwave-based WBH approach for metastasis inhibition is established and its typical results are discussed.
  
  
  METHODS
  The effectiveness of a 30-min whole body hyperthermia (WH) on animals, raised to a rectal temperature of 40.2° ± 0.3°C for 30  min followed by 84 h observation by 2450 MHz microwave irradiation, were evaluated. In an experimental lung metastasis model by injection of B16-F10 melanoma, lungs were removed from sacrificed mice 16 days after tumour implantation, and the expression of heat shock protein, inter-cellular adhesion molecule 1 (ICAM-1), proliferating cell nuclear antigen (PCNA) and cyclin D(1) was examined. CD4(+), CD8(+) and NK cell subpopulation in peripheral blood were measured by flow cytometry before and after the last treatment.
  
  
  RESULTS
  The best therapeutic effect was obtained when the mice were treated with WBH in combination with the initial chemotherapy with cis-diaminodichloroplatinum (CDDP) and dacarbazine (DTIC) (p < 0.05). The WBH alone has an advantage of reduced toxicity and lower cost. Heat shock protein (HSP) expression increased in the hyperthermia groups. Reduction of PCNA and cyclin D(1) was observed in the mice treated with WH alone or in combination with chemotherapy. In the hyperthermia groups, CD4(+)/CD8(+) decreased while the NK increased slightly.
  
  
  CONCLUSIONS
  The whole body hyperthermia protocol described in this work inhibits B16 tumour metastasis by inhibiting cell proliferation, neovascularisation and stimulating favourable immune responses. It demonstrated that WBH treatment benefits therapy of metastasis cancers.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, P.R. China.
authors.forename: Dewei
authors.initials: D
authors.lastname: Jia
authors.forename: Wei
authors.initials: W
authors.lastname: Rao
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Jin
authors.forename: Suqiong
authors.initials: S
authors.lastname: Wang
authors.forename: Dongwei
authors.initials: D
authors.lastname: Chen
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.forename: Junwei
authors.initials: J
authors.lastname: Guo
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003606:Dacarbazine / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000276:immunology; D006979:Hyperthermia, Induced / Q000379:methods*; D007109:Immunity / Q000276:immunology*; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D002945:Cisplatin