BACKGROUND AND PURPOSE: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. METHODS AND MATERIALS: In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1α (HIF-1α) in cancer was determined by immunofluorescence. RESULTS: Among biopsy specimens taken before castration, strong HIF-1α expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1α (mean intensity 0-10) in 6 patients. Downregulation of HIF-1α expression after castration was observed in all 5 patients with strong HIF-1α precastration expression. HIF-1α expression was also reduced in 2 of 3 patients with weak HIF-1α precastration expression. CONCLUSIONS: Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.
BACKGROUND AND PURPOSE: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. METHODS AND MATERIALS: In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1α (HIF-1α) in cancer was determined by immunofluorescence. RESULTS: Among biopsy specimens taken before castration, strong HIF-1α expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1α (mean intensity 0-10) in 6 patients. Downregulation of HIF-1α expression after castration was observed in all 5 patients with strong HIF-1α precastration expression. HIF-1α expression was also reduced in 2 of 3 patients with weak HIF-1α precastration expression. CONCLUSIONS: Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.
Authors: Kwanghee Kim; Philip A Watson; Souhil Lebdai; Sylvia Jebiwott; Alexander J Somma; Stephen La Rosa; Dipti Mehta; Katie S Murray; Hans Lilja; David Ulmert; Sebastien Monette; Avigdor Scherz; Jonathan A Coleman Journal: Clin Cancer Res Date: 2018-02-20 Impact factor: 12.531
Authors: Austin N Kirschner; Jie Wang; Riet van der Meer; Philip D Anderson; Omar E Franco-Coronel; Max H Kushner; Joel H Everett; Omar Hameed; Erika K Keeton; Miika Ahdesmaki; Shaun E Grosskurth; Dennis Huszar; Sarki A Abdulkadir Journal: J Natl Cancer Inst Date: 2014-12-13 Impact factor: 13.506