Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression

Shang Zhiqun; Li Yanjun; Zhang Minghao; Tian Jing; Han Ruifa; Shyr Chih-Rong; Messing Edward; Yeh Shuyuan; Niu Yuanjie; Chang Chawnshang

首页> 外文期刊>Molecular cancer therapeutics >Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression

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Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression

机译：抗羟基氟胺或雄激素受体降解增强剂ASC-J9的抗抗原疗法增强了BCG效果，以更好地抑制膀胱癌进展

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Recent studies suggest that the androgen receptor (AR) might play important roles in influencing bladder cancer progression, yet its clinical application remains unclear. Here, we developed a new combined therapy with Bacillus Calmette-Guerin (BCG) and the AR degradation enhancer ASC-J9 or antiandrogen hydroxyflutamide (HF) to better suppress bladder cancer progression. Mechanism dissection revealed that ASC-J9 treatment enhanced BCG efficacy to suppress bladder cancer cell proliferation via increasing the recruitment of monocytes/macrophages that involved the promotion of BCG attachment/internalization to the bladder cancer cells through increased integrin-alpha 5 beta 1 expression and IL6 release. Such consequences might then enhance BCG-induced bladder cancer cell death via increased TNF alpha release. Interestingly, we also found that ASC-J9 treatment could directly promote BCG-induced HMGB1 release to enhance the BCG cytotoxic effects for suppression of bladder cancer cell growth. In vivo approaches also concluded that ASC-J9 could enhance the efficacy of BCG to better suppress bladder cancer progression in BBN-induced bladder cancer mouse models. Together, these results suggest that the newly developed therapy combining BCG plus ASC-J9 may become a novel therapy to better suppress bladder cancer progress. (C) 2015 AACR.

机译：最近的研究表明，雄激素受体（AR）可能在影响膀胱癌进展方面发挥重要作用，但其临床应用尚不清楚。在这里，我们开发了芽孢杆菌（BCG）和ar降解增强剂ASC-J9或抗酸羟基氟胺（HF）的新组合疗法，以更好地抑制膀胱癌进展。机制解剖表明，ASC-J9治疗通过增加通过增加的整联蛋白-α5表达和IL6增加促进BCG附着/内化对膀胱癌细胞的单核细胞/巨噬细胞来抑制BCG癌细胞增殖的BCG疗效增强了BCG癌细胞增殖。释放。然后，这种后果可以通过增加的TNFα释放来增强BCG诱导的膀胱癌细胞死亡。有趣的是，我们还发现ASC-J9治疗可以直接促进BCG诱导的HMGB1释放，以增强BCG细胞毒性效应，以抑制膀胱癌细胞生长。体内方法也得出结论，ASC-J9可以提高BCG在BBN诱导的膀胱癌小鼠模型中更好地抑制膀胱癌进展的疗效。这些结果表明，结合BCG Plus ASC-J9的新开发的治疗可能成为一种更好地抑制膀胱癌进展的新疗法。（c）2015年AACR。

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《Molecular cancer therapeutics》 |2015年第11期|共9页
作者
Shang Zhiqun; Li Yanjun; Zhang Minghao; Tian Jing; Han Ruifa; Shyr Chih-Rong; Messing Edward; Yeh Shuyuan; Niu Yuanjie; Chang Chawnshang;
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Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Univ Rochester Med Ctr George Whipple Lab Canc Res Dept Pathol Rochester NY 14642 USA;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

Tianjin Med Univ Hosp 2 Chawnshang Chang Sex Hormone Res Ctr Tianjin Inst Urol Tianjin 300211;

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1. Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression [J] . Shang Zhiqun, Li Yanjun, Zhang Minghao, Molecular cancer therapeutics . 2015,第11期

机译：抗羟基氟胺或雄激素受体降解增强剂ASC-J9的抗抗原疗法增强了BCG效果，以更好地抑制膀胱癌进展
2. Preclinical study using androgen receptor (AR) degradation enhancer to increase radiotherapy efficacy via targeting radiation-increased AR to better suppress prostate cancer progression [J] . Fu-Ju Chou, Yuhchyau Chen, Dong Chen, EBioMedicine . 2019,第184期

机译：临床前研究使用雄激素受体（AR）降解增强剂通过靶向放射增高的AR更好地抑制前列腺癌的进展来提高放射治疗的功效
3. Targeting the androgen receptor (AR) with AR degradation enhancer ASC-J9 (R) led to increase docetaxel sensitivity via suppressing the p21 expression [J] . Luo Jie, Tian Jing, Chou FuJu, Cancer letters . 2019,第期

机译：用Ar降解增强剂ASC-J9（R）靶向雄激素受体（AR），导致通过抑制P21表达增加多西紫杉醇敏感性
4. Optimal Control on Bladder Cancer Growth Model with BCG Immunotherapy and Chemotherapy [C] . C. Dewi, Trisilowati Symposium on Biomathematics . 2015

机译：BCG免疫疗法和化疗对膀胱癌生长模型的最佳控制
5. Development of pan-antagonists of mutant androgen receptors associated with antiandrogen resistant prostate cancer. [D] . Pan, Hongmu. 2009

机译：与抗雄激素抵抗性前列腺癌有关的突变雄激素受体泛拮抗剂的发展。
6. Anti-androgen therapy with Hydroxyflutamide or androgen receptor degradation enhancer ASC-J9® enhances BCG efficacy to better suppress bladder cancer progression [O] . Zhiqun Shang, Yanjun Li, Minghao Zhang, -1

机译：羟基氟他胺或雄激素受体降解促进剂ASC-J9®的抗雄激素疗法可增强BCG功效从而更好地抑制膀胱癌的进展
7. Preclinical Study using Malat1 Small Interfering RNA or Androgen Receptor Splicing Variant 7 Degradation Enhancer ASC-J9 ® to Suppress Enzalutamide-resistant Prostate Cancer Progression [O] . Ronghao Wang, Yin Sun, Lei Li, 2017

机译：使用MALAT1小干扰RNA或雄激素受体剪接变体7降解增强剂ASC-J9®的临床前研究，用于抑制抗甲醛抗性前列腺癌进展

Antiandrogen Therapy with Hydroxyflutamide or Androgen Receptor Degradation Enhancer ASC-J9 Enhances BCG Efficacy to Better Suppress Bladder Cancer Progression

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