Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides.
Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides.
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通过比例可激活的细胞穿透性肽，在致癌物诱导口腔癌啮齿动物模型中对鳞状细胞癌的早期检测。
DOI：
10.1016/j.oraloncology.2017.06.009
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发表时间：
2017-08
期刊：
影响因子：
4.8
通讯作者：
Nguyen QT
中科院分区：
文献类型：
--
作者：
Hingorani DV;Lemieux AJ;Acevedo JR;Glasgow HL;Kedarisetty S;Whitney MA;Molinolo AA;Tsien RY;Nguyen QT
比率计量型细胞穿透肽(RACPP)是一种发夹状分子，可被肿瘤相关蛋白酶裂解，导致可测量的Cy5：Cy7荧光比率变化来标记体内的癌症。在致癌物诱导的啮齿动物肿瘤模型中，我们评估了一种可裂解的基质金属蛋白酶RACPP用于早期检测恶性病变。野生型免疫活性小鼠给予4-硝基喹啉氧化物(4NQO)16周。从第11周到第21周，使用白光反射和Cy5：Cy7比率荧光对静脉注射可裂解的MPPLGC(Me)AG-RACPP的活体小鼠的口腔进行了连续成像。在最初的研究中，我们发现在第21周，几乎所有的小鼠(13/14)都有口腔病变，其中90%是高度不典型增生或浸润性癌。白光反射和RACPPCy5：Cy7比值荧光检测高度恶性病变，两者的检测率相近，RACPP的曲线下面积(AUC)为0.97(95%可信区间=0.92~1.02，p<；0.001)，敏感性=%，特异性=100%。在后续研究中，在第16、18和21周对4NQO引起的口腔病变进行成像和组织学分析。在这项研究中，我们发现RACPP-荧光检测阳性地识别了15个鳞状细胞癌(在6个单独的小鼠中)，这些鳞状细胞癌在白色光反射中很难被察觉或无法检测到。RACPP比率荧光可以用来准确地检测免疫活性小鼠中致癌物质诱导的癌症，这些小鼠的白色光反射很难看到或无法检测到。
Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in-vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model. Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16 weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence. In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI) = 0.92–1.02, p<0.001), sensitivity = 89%, specificity =100%. In a follow up study, oral cavity lesions generated by 4NQO were imaged and histologically analyzed at weeks 16,18 and 21. In this study we showed that RACPP-fluorescence detection positively identified 15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or undetectable by white light reflectance. RACPP ratiometric fluorescence can be used to accurately detect carcinogen-induced carcinoma in immunocompetent mice that are poorly visible or undetectable by white light reflectance.
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影响因子：
3.3
作者：
Czeminski, Rakefet;Amornphimoltham, Panomwat;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio
影响因子：
2.6
作者：
Mallis, Antony;Teymoortash, Afshin;Papadas, Theodoros A.
通讯作者：
Papadas, Theodoros A.
影响因子：
7.7
作者：
Muto, M;Hironaka, S;Yoshida, S
通讯作者：
Yoshida, S
DOI：
10.1002/hed.23838
发表时间：
2016-01-01
影响因子：
2.9
作者：
Kraft, Marcel;Fostiropoulos, Karolos;Arens, Christoph
通讯作者：
Arens, Christoph
DOI：
10.1039/b904890a
发表时间：
2009-06
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Olson ES;Aguilera TA;Jiang T;Ellies LG;Nguyen QT;Wong EH;Gross LA;Tsien RY
通讯作者：
Tsien RY