A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer.
A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer.
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DOI：
10.1126/scitranslmed.3004334
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发表时间：
2012-10-17
影响因子：
17.1
通讯作者：
Saluja AK
中科院分区：
文献类型：
--
作者：
Chugh R;Sangwan V;Patil SP;Dudeja V;Dawra RK;Banerjee S;Schumacher RJ;Blazar BR;Georg GI;Vickers SM;Saluja AK
胰腺癌是最致命的人类恶性肿瘤之一，全阶段5年生存率<5%，这突出了对更有效治疗策略的迫切需求。我们以前已经表明，雷公藤内酯醇，二萜类化合物，是有效的对胰腺癌细胞在体外以及在体内。然而，雷公藤内酯醇在水中溶解性差，限制了其临床应用。因此，我们合成了一种水溶性类似物雷公藤内酯醇，命名为Minnelide。在体外和多个独立但互补的胰腺癌体内模型中测试了Minnelide的疗效：在无胸腺裸鼠中使用人胰腺癌细胞系的原位胰腺癌模型，将人胰腺肿瘤移植到严重联合免疫缺陷小鼠中的异种移植模型，以及自发性胰腺癌小鼠模型（KRasG 12 D; Trp 53 R172 H; Pdx-1Cre）。在这些胰腺癌的多种互补模型中，Minnelide在减少胰腺肿瘤生长和扩散以及提高生存率方面非常有效。总之，我们的研究结果表明，Minnelide显示出作为一种有效的胰腺癌化疗药物的前景，并支持Minnelide在临床试验中对这种致命疾病的评估。
Pancreatic cancer is one of the most lethal human malignancies with an all-stage 5-year survival frequency of <5%, which highlights the urgent need for more effective therapeutic strategies. We have previously shown that triptolide, a diterpenoid, is effective against pancreatic cancer cells in vitro as well as in vivo. However, triptolide is poorly soluble in water, limiting its clinical use. We therefore synthesized a water-soluble analog of triptolide, named Minnelide. The efficacy of Minnelide was tested both in vitro and in multiple independent yet complementary in vivo models of pancreatic cancer: an orthotopic model of pancreatic cancer using human pancreatic cancer cell lines in athymic nude mice, a xenograft model where human pancreatic tumors were transplanted into severe combined immunodeficient mice, and a spontaneous pancreatic cancer mouse model (KRasG12D; Trp53R172H; Pdx-1Cre). In these multiple complementary models of pancreatic cancer, Minnelide was highly effective in reducing pancreatic tumor growth and spread, and improving survival. Together, our results suggest that Minnelide shows promise as a potent chemotherapeutic agent against pancreatic cancer, and support the evaluation of Minnelide in clinical trials against this deadly disease.
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DOI：
10.1016/j.jss.2010.03.067
发表时间：
2010-10
期刊：
The Journal of surgical research
影响因子：
--
作者：
Clawson KA;Borja-Cacho D;Antonoff MB;Saluja AK;Vickers SM
通讯作者：
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影响因子：
6.4
作者：
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影响因子：
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通讯作者：
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影响因子：
45.3
作者：
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影响因子：
50.3
作者：
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