Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model.
Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model.
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DOI：
10.1038/pcan.2010.52
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发表时间：
2011-06
影响因子：
4.8
通讯作者：
Baust, J. G.
中科院分区：
文献类型：
--
作者：
Santucci, K. L.;Snyder, K. K.;Baust, J. M.;Van Buskirk, R. G.;Mouraviev, V.;Polascik, T. J.;Gage, A. A.;Baust, J. G.
冷冻疗法已成为前列腺癌（CaP）的主要治疗选择;然而，冷冻病变周围的不完全消融可能导致复发。因此，我们研究了使用无毒的抗氧化剂维生素D3与冷冻疗法来使CaP对低温诱导的非冰破裂相关的细胞死亡敏感。维生素D3（骨化三醇）已被确定为一种可能的辅助治疗癌症，由于其抗增殖和抗肿瘤的性质。本研究旨在确定维生素D3（骨化三醇）与冷冻疗法结合在小鼠前列腺癌模型中激活的细胞反应和分子途径。高于-15 °C的单次冻融事件对癌细胞活力几乎没有影响;然而，用骨化三醇预处理结合冷冻显著增加了细胞死亡。在单次冷冻后，-15 °C的骨化三醇组合使细胞死亡增加至55%，相比之下，冷冻或单独骨化三醇的细胞损失可以忽略不计。重复冷冻组合产生了90%的细胞死亡，相比之下，双冷冻循环中的细胞死亡率为65%。骨化三醇冷冻增敏方案后的蛋白质印迹分析证实了细胞凋亡的激活。具体而言，发现促凋亡Bid和半胱天冬酶原-3在组合处理后1小时降低，表明裂解为活性形式。一项平行的体内研究证实，当冷冻疗法与骨化三醇预处理组合时，细胞死亡增加。骨化三醇和冷冻疗法相结合的连续疗法的发展代表了一种潜在的高效、低毒、微创治疗选择。这些结果表明骨化三醇和冷冻作为具有临床转化潜力的CaP的组合治疗的作用。
Cryotherapy has emerged as a primary treatment option for prostate cancer(CaP); however, incomplete ablation in the periphery of the cryogenic lesion can lead to recurrence. Accordingly, we investigated the use of a nontoxic adjunctive agent, Vitamin D3, with cryotherapy to sensitize CaP to low temperature induced, non-ice rupture related cell death. Vitamin D3 (calcitriol) has been identified as a possible adjunct in the treatment of cancer due to its anti-proliferative and anti-tumorigenic properties. This study aimed to identify the cellular responses and molecular pathways activated when vitamin D3 (calcitriol) is combined with cryotherapy in a murine prostate cancer model. Single freeze-thaw events above −15°C had little effect on cancer cell viability; however, pre-treatment with calcitriol in conjunction with cryo significantly increased cell death. The −15°C calcitriol combination increased cell death to 55% following a single freeze, compared to negligible cell loss by freezing or calcitriol alone. Repeat cryo-combination yielded90% cell death, compared to 65% in dual freeze-only cycles. Western blot analysis following calcitriol cryosensitization regimes confirmed the activation of apoptosis. Specifically, pro-apoptotic Bid and pro-caspase–3 were found to decrease at 1h following combination treatment, indicating cleavage to the active forms. A parallel in vivo study confirmed the increased cell death when combining cryotherapy with calcitriol pre-treatment. The development of an adjunctive therapy combining calcitriol and cryotherapy represents a potentially highly effective, less toxic, minimally invasive treatment option. These results suggest a role for calcitriol and cryo as a combinatorial treatment for CaP with the potential for clinical translation.
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影响因子：
2.7
作者：
Clarke, DM;Baust, JM;Baust, JG
通讯作者：
Baust, JG
DOI：
10.1016/s1078-1439(03)00170-4
发表时间：
2003-09-01
影响因子：
2.7
作者：
Beer, TM
通讯作者：
Beer, TM
影响因子：
2.7
作者：
Baust, JG;Gage, AA;Van Buskirk, R
通讯作者：
Van Buskirk, R
影响因子：
4.8
作者：
Narvaez, CJ;Welsh, J
通讯作者：
Welsh, J
DOI：
10.1016/0960-0760(95)00001-g
发表时间：
1995-05-01
影响因子：
4.1
作者：
BALEY, PA;YOSHIDA, K;THOMPSON, TC
通讯作者：
THOMPSON, TC