title: Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice.
abstract: OBJECTIVE
  To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy and thermochemoradiotherapy.
  
  
  METHODS
  Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43 centigrade, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy, radiotherapy, thermochemotherapy, thermoradiotherapy, and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining.
  
  
  RESULTS
  All of the six treatment modalities down-regulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 +/- 0.009 vs 0.155 +/- 0.0115, P < 0.01) and Bcl-2 (0.086 +/- 0.010 vs 0.026 +/- 0.0170, P < 0.01) and up-regulating Bax expression (0.091 +/- 0.0013 vs 0.207 +/- 0.027, P < 0.01) compared with any single therapy.
  
  
  CONCLUSIONS
  Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.
authors: Department of Gastrointestinal Oncological Surgery, Tianjin Cancer Hospital, Tianjin Medical University, Tibyanbei Hexi District, Tianjin 300060, China. tjlianghan@126.com
authors: Han
authors: H
authors: Liang
authors: Hong-Jie
authors: HJ
authors: Zhan
authors: Bao-Gui
authors: BG
authors: Wang
authors: Yuan
authors: Y
authors: Pan
authors: Xi-Shan
authors: XS
authors: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D008297:Male; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011878:Radiotherapy / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein
references: Cancer Gene Ther. 1999 Mar-Apr;6(2):155-62
references: 10195882
references: Int J Hyperthermia. 2003 Nov-Dec;19(6):590-7
references: 14756450
references: Clin Cancer Res. 1995 Feb;1(2):139-45
references: 9815966
references: Nature. 1993 Apr 29;362(6423):847-9
references: 8479522
references: Gene. 2004 May 26;333:71-9
references: 15177682
references: Int J Hyperthermia. 2005 Dec;21(8):761-7
references: 16338859
references: Cell. 1993 Sep 24;74(6):957-67
references: 8402885
references: Cancer Gene Ther. 2000 Jun;7(6):885-92
references: 10880019
references: Semin Oncol. 2002 Jun;29(3):246-57
references: 12063677
references: Curr Opin Oncol. 1995 Nov;7(6):541-6
references: 8547403
references: Zhonghua Yi Xue Za Zhi. 2004 Aug 2;84(15):1299-303
references: 15387970
references: J Natl Cancer Inst. 1994 Oct 5;86(19):1458-62
references: 8089864
references: Chin Med J (Engl). 2005 Dec 20;118(24):2093-6
references: 16438908
references: Blood. 1997 Apr 15;89(8):2986-93
references: 9108419
references: Cancer Res. 1993 Jul 15;53(14):3321-6
references: 8324744
references: Oncol Rep. 2005 Sep;14(3):609-15
references: 16077963
references: Int J Clin Oncol. 2001 Jun;6(3):138-42
references: 11706783