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新型荧光试剂可检测出微小卵巢肿瘤

标签:荧光试剂 肿瘤
摘要 : 3月30日日本东京大学等机构研究人员近日在英国《自然·通讯》杂志上报告说,他们开发出一种新型荧光试剂,在卵巢癌诊断中可检测出1毫米以下的微小肿瘤,有助提高卵巢癌手术的效果。

 3月30日日本东京大学等机构研究人员近日在英国《自然·通讯》杂志上报告说,他们开发出一种新型荧光试剂,在卵巢癌诊断中可检测出1毫米以下的微小肿瘤,有助提高卵巢癌手术的效果。

据介绍,在通过手术切除卵巢癌肿瘤时,如能切除1毫米以下的微小肿瘤,治疗效果将大幅提高。但是,这些微小的肿瘤却很难与正常组织区分开来。

东京大学教授浦野泰照等人报告说,他们开发了一种名为“gGlu-HMRG”的荧光试剂,这种试剂本身无色透明,但在与卵巢癌细胞中的“β-半乳糖苷酶”发生反应后,就会发出强烈荧光。

动物实验显示,在向患有卵巢癌的实验鼠体内存在肿瘤的部位喷洒这种荧光试剂后,存在癌细胞的地方数分钟后就能发出非常明亮的荧光,用肉眼便可观察到,能高精度检测出不到1毫米的微小肿瘤。研究小组以荧光为标记,成功切除了肿瘤。

研究小组认为,由于检测时只需喷洒微量的试剂,所以副作用很小。如果改善试剂使其还能与其他种类的酶结合,这种试剂还有望用于检测其他种类的癌细胞。

研究小组准备进一步验证这种试剂的精确度和安全性,争取在3至5年后开展临床试验。

Sensitive ​β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo

Abstract

Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on ​β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular ​β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as <1 mm in diameter in seven mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3, OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real-time detection of metastases with the naked eye is possible. Endoscopic fluorescence detection of metastases is also demonstrated. The results clearly indicate preclinical potential value of the probe for fluorescence-guided diagnosis of peritoneal metastases from ovarian cancers.

来源: Nature Communications 浏览次数:66

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