Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers.,Nature Biomedical Engineering

当前位置： X-MOL 学术 › Nat. Biomed. Eng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Validation of the use of a fluorescent PARP1 inhibitor for the detection of oral, oropharyngeal and oesophageal epithelial cancers.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2020-03-12 , DOI: 10.1038/s41551-020-0526-9
Susanne Kossatz _{1,

2} , Giacomo Pirovano ₁ , Paula Demétrio De Souza França ₁ , Arianna L Strome ₁ , Sumsum P Sunny _{3,

4} , Daniella Karassawa Zanoni ₅ , Audrey Mauguen ₆ , Brandon Carney ₁ , Christian Brand _{1,

7} , Veer Shah ₁ , Ravindra D Ramanajinappa ₃ , Naveen Hedne ₄ , Praveen Birur _{3,

8} , Smita Sihag ₅ , Ronald A Ghossein ₉ , Mithat Gönen ₆ , Marshall Strome ₁₀ , Amritha Suresh ₃ , Daniela Molena ₅ , Ian Ganly ₅ , Moni A Kuriakose _{3,

11} , Snehal G Patel ₅ , Thomas Reiner _{1,

12,

13}

Affiliation

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Nuclear Medicine, University Hospital Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
Integrated Head and Neck Oncology Research Program, Mazumdar Shaw Medical Foundation, Narayana Health, Bengaluru, India.
Head and Neck Oncology, Mazumdar Shaw Medical Center, Narayana Health, Bengaluru, India.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Summit Biomedical Imaging, New York, NY, USA.
Department of Oral Medicine and Radiology, KLES Institute of Dental Sciences, Bangalore, India.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Head and Neck Surgical Group, New York, NY, USA.
Cochin Cancer Research Center, Kochi, India.
Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labelled small-molecule inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) for the detection of cancers of the oral cavity, pharynx and oesophagus. We show that the fluorescent contrast agent can be used to quantify the expression levels of PARP1 and to detect oral, oropharyngeal and oesophageal tumours in mice, pigs and fresh human biospecimens when delivered topically or intravenously. The fluorescent PARP1 inhibitor can also detect oral carcinoma in a patient when applied as a mouthwash, and discriminate between fresh biopsied samples of the oral tumour and the surgical resection margin with more than 95% sensitivity and specificity. The PARP1 inhibitor could serve as the basis of a rapid and sensitive assay for the early detection and for the surgical-margin assessment of epithelial cancers of the upper intestinal tract.

中文翻译：

验证使用荧光 PARP1 抑制剂检测口腔癌、口咽癌和食管上皮癌。

对于口腔癌、口咽癌和食管癌，肿瘤和术后残留肿瘤的早期发现是复发率和患者生存的预后因素。在这里，我们报告了在动物模型和人类中使用先前描述的 DNA 修复酶聚（ADP-核糖）聚合酶 1 (PARP1) 的荧光标记小分子抑制剂来检测癌症的验证。口腔、咽部和食道。我们表明，当局部或静脉注射时，荧光造影剂可用于量化 PARP1 的表达水平，并检测小鼠、猪和新鲜人类生物样本中的口腔、口咽和食管肿瘤。当用作漱口水时，荧光 PARP1 抑制剂还可以检测患者的口腔癌，并以超过 95% 的敏感性和特异性区分口腔肿瘤的新鲜活检样本和手术切除边缘。 PARP1 抑制剂可以作为快速、灵敏检测的基础，用于上肠道上皮癌的早期检测和手术边缘评估。

更新日期：2020-04-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文