Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness.
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness.
复制标题
DOI：
10.1038/s41598-017-06534-z
复制
发表时间：
2017-08-08
影响因子：
4.6
通讯作者：
Ohuchi N
中科院分区：
文献类型：
--
作者：
Gonda K;Watanabe M;Tada H;Miyashita M;Takahashi-Aoyama Y;Kamei T;Ishida T;Usami S;Hirakawa H;Kakugawa Y;Hamanaka Y;Yoshida R;Furuta A;Okada H;Goda H;Negishi H;Takanashi K;Takahashi M;Ozaki Y;Yoshihara Y;Nakano Y;Ohuchi N
由于酶活性会影响IHC- dab显色反应，医院病理诊断中使用的常规免疫组织化学（IHC） 3,3′-二氨基联苯胺（IHC- dab）的定量灵敏度和动态范围较差。虽然荧光免疫组化可以有效提高常规免疫组化的定量灵敏度，但组织自身荧光会干扰灵敏度。在这里，我们创造了新的荧光纳米粒子，称为磷集成点（pid）。与商业上可用的荧光纳米粒子量子点相比，pid的亮度要高100倍，动态范围要大300倍以上，量子点的荧光强度与组织自身荧光相当。此外，一种新开发的图像处理方法可以计算得到的图像中的PID粒子数。为了量化IHC检测的灵敏度（IHC- pid），我们将IHC- pid与荧光活化细胞分选（FACS）进行了比较，后者是一种非常适合评估总蛋白量的方法，两者具有很强的相关性（R = 0.94）。接下来，我们应用ihc - pid对乳腺癌患者对分子靶向药物治疗的反应进行分类。结果提示化疗前活检获得的乳腺癌组织ihc -PID估计的PID颗粒数可以为预测人表皮生长因子受体2靶向药物曲妥珠单抗的治疗效果提供评分。
The quantitative sensitivity and dynamic range of conventional immunohistochemistry (IHC) with 3,3′-diaminobenzidine (IHC-DAB) used in pathological diagnosis in hospitals are poor, because enzyme activity can affect the IHC-DAB chromogenic reaction. Although fluorescent IHC can effectively increase the quantitative sensitivity of conventional IHC, tissue autofluorescence interferes with the sensitivity. Here, we created new fluorescent nanoparticles called phosphor-integrated dots (PIDs). PIDs have 100-fold greater brightness and a more than 300-fold greater dynamic range than those of commercially available fluorescent nanoparticles, quantum dots, whose fluorescence intensity is comparable to tissue autofluorescence. Additionally, a newly developed image-processing method enabled the calculation of the PID particle number in the obtained image. To quantify the sensitivity of IHC using PIDs (IHC-PIDs), the IHC-PIDs method was compared with fluorescence-activated cell sorting (FACS), a method well suited for evaluating total protein amount, and the two values exhibited strong correlation (R = 0.94). We next applied IHC-PIDs to categorize the response to molecular target-based drug therapy in breast cancer patients. The results suggested that the PID particle number estimated by IHC-PIDs of breast cancer tissues obtained from biopsy before chemotherapy can provide a score for predicting the therapeutic effect of the human epidermal growth factor receptor 2-targeted drug trastuzumab.
登录
查看更多内容
影响因子：
4.6
作者：
Gonda K;Miyashita M;Higuchi H;Tada H;Watanabe TM;Watanabe M;Ishida T;Ohuchi N
通讯作者：
Ohuchi N
影响因子：
168.9
作者：
Gianni, Luca;Eiermann, Wolfgang;Baselga, Jose
通讯作者：
Baselga, Jose
DOI：
10.1016/s1470-2045(13)70130-x
发表时间：
2013-05
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Swain SM;Kim SB;Cortés J;Ro J;Semiglazov V;Campone M;Ciruelos E;Ferrero JM;Schneeweiss A;Knott A;Clark E;Ross G;Benyunes MC;Baselga J
通讯作者：
Baselga J
影响因子：
3.5
作者：
Hikage, Makoto;Gonda, Kohsuke;Ohuchi, Noriaki
通讯作者：
Ohuchi, Noriaki
影响因子：
7.5
作者：
Provenzano, Elena;Bossuyt, Veerle;Symmans, W. Fraser
通讯作者：
Symmans, W. Fraser