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首页> 外文期刊>Cancer prevention research. >A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer
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A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer

机译：早期乳腺癌患者口服水飞蓟宾-磷脂酰胆碱的术前研究

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Silybin-phosphatidylcholine is an orally bioavailable complex of silybin, a polyphenolic flavonolignan derived from milk thistle, endowed with potential anticancer activity in preclinical models. The purpose of this window of opportunity trial was to determine, for the first time in early breast cancer patients, the breast tissue distribution of silybin. Twelve breast cancer patients received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery. Silybin levels were measured before (SIL) and after (TOT-SIL) enzymatic hydrolysis by high-performance liquid chromatography (HPLC)-MS/MS in biologic samples (plasma, urine, breast cancer, and surrounding normal tissue). Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. All patients were fully compliant and completed the treatment program. No toxicity was observed. SIL and TOT-SIL were undetectable in baseline samples. Despite a high between-subject variability, repeated administration of Siliphos achieved levels of TOT-SIL of 31,121 to 7,654 ng/mL in the plasma and up to 1,375 ng/g in breast cancer tissue. SIL concentrations ranged from 10,861 to 1,818 ng/mL in plasma and up to 177 ng/g in breast cancer tissue. Median TOT-SIL concentration was higher in the tumor as compared with the adjacent normal tissue (P = 0.018). No significant change in either blood levels of IGF-I and nitric oxide or Ki-67 in tumors was noted. Silybin-phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue. These findings provide the basis for a future phase II biomarker trial in breast cancer prevention. (C)2015 AACR.
机译：水飞蓟宾-磷脂酰胆碱是水飞蓟宾的口服生物利用复合物，水飞蓟宾是一种源自乳蓟的多酚类黄酮木脂素，在临床前模型中具有潜在的抗癌活性。该机会窗口试验的目的是首次确定早期乳腺癌患者中水飞蓟宾的乳腺组织分布。十二名乳腺癌患者在手术前4周每天接受2.8 g的水飞蓟宾磷脂酰胆碱治疗。通过高效液相色谱（HPLC）-MS / MS测定生物样品（血浆，尿液，乳腺癌和周围正常组织）中（SIL）酶水解之前（SIL）和（TOT-SIL）之后的水飞蓟宾水平。在基线，最后一次给药之前和2小时后采集空腹血液样品。所有患者均完全依从并完成了治疗方案。没有观察到毒性。在基线样品中未检测到SIL和TOT-SIL。尽管受试者之间存在很高的变异性，但重复施用Siliphos可使血浆中TOT-SIL的水平达到31,121至7,654 ng / mL，而在乳腺癌组织中达到最高1,375 ng / g。血浆中的SIL浓度范围为10,861至1,818 ng / mL，乳腺癌组织中的SIL浓度最高为177 ng / g。与邻近的正常组织相比，肿瘤中的TOT-SIL浓度更高（P = 0.018）。肿瘤中IGF-I和一氧化氮或Ki-67的血液水平均未见明显变化。口服水飞蓟宾磷脂酰胆碱可以递送高浓度的水飞蓟宾，水飞蓟宾可选择性地积聚在乳腺肿瘤组织中。这些发现为将来在预防乳腺癌中进行的II期生物标志物试验提供了基础。 （C）2015 AACR。

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