Abstract
Objectives: Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer. Methods: Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses. Results: Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment. Conclusions: The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation.
| Original language | English |
|---|---|
| Journal | Urology |
| Volume | 76 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2010 |
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ASJC Scopus subject areas
- Urology
Cite this
Role of vitamin D3 as a sensitizer to cryoablation in a murine prostate cancer model : Preliminary in vivo study. / Kimura, Masaki; Rabbani, Zahid; Mouraviev, Vladimir; Tsivian, Matvey; Caso, Jorge; Satoh, Takefumi; Baba, Shiro; Vujaskovic, Zeljko; Baust, John M.; Baust, John G.; Polascik, Thomas J.
In: Urology, Vol. 76, No. 3, 01.09.2010.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of vitamin D3 as a sensitizer to cryoablation in a murine prostate cancer model
T2 - Preliminary in vivo study
AU - Kimura, Masaki
AU - Rabbani, Zahid
AU - Mouraviev, Vladimir
AU - Tsivian, Matvey
AU - Caso, Jorge
AU - Satoh, Takefumi
AU - Baba, Shiro
AU - Vujaskovic, Zeljko
AU - Baust, John M.
AU - Baust, John G.
AU - Polascik, Thomas J.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Objectives: Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer. Methods: Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses. Results: Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment. Conclusions: The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation.
AB - Objectives: Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer. Methods: Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses. Results: Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment. Conclusions: The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation.
UR - http://www.scopus.com/inward/record.url?scp=79956126437&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956126437&partnerID=8YFLogxK
U2 - 10.1016/j.urology.2010.03.041
DO - 10.1016/j.urology.2010.03.041
M3 - Article
C2 - 20599255
AN - SCOPUS:79956126437
VL - 76
JO - Urology
JF - Urology
SN - 0090-4295
IS - 3
ER -