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大鼠腭黏膜化学诱导的癌前病变和鳞状细胞癌的体内光检测

In vivo photo-detection of chemically induced premalignant lesions and squamous cell carcinoma of the rat palatal mucosa.

作者信息

Nauta J M, Speelman O C, van Leengoed H L, Nikkels P G, Roodenburg J L, Star W M, Witjes M J, Vermey A

机构信息

Department of Oral and Maxillofacial Surgery, University Hospital Groningen, Netherlands.

出版信息

J Photochem Photobiol B. 1997 Jun;39(2):156-66. doi: 10.1016/s1011-1344(96)00011-5.

Abstract

Photo-detection using in vivo fluorescence was studied for different stages of chemically induced premalignant lesions and squamous cell carcinoma (SCC) of the Wistar rat palatal mucosa. It was found that the epithelial dysplasia (numerically expressed in the epithelial atypia index (EAI) of the rat palate, induced by repeated application of the carcinogen 4-nitroquinoline 1-oxide (4NQO), showed an increase approximately proportional to the duration of the application period. Photo-detection of the lesions using Photofrin-induced fluorescence was studied with dual-wavelength excitation and the subtraction of images, in an attempt to reduce the autofluorescence. The Photofrin dose was 2.5 mg kg-1. This was based on a dose-response study for normal tissue damage by photodynamic therapy (PDT) in this animal model, because the underlying rationale was to study photo-detection as a method of locating additional (early) malignancies in patients treated by PDT. Fluorescence intensities 24 and 48 h after injection of Photofrin were shown to increase with the duration of 4NQO application and with increasing EAI. For an EAI greater than 15, there was a statistically significant difference (p < 0.01) between the fluorescence signals obtained with and without the injection of Photofrin. Fluorescence signals of these lesions without the use of Photofrin (autofluorescence) also showed an increase with increasing stages of epithelial dysplasia of the rat palate. However, the fluorescence signals obtained with Photofrin were always higher than those of the autofluorescence. From this study, we conclude that photo-detection with Photofrin has potential in distinguishing chemically induced premalignant lesions and squamous cell carcinomas from the normal rat palatal mucosa. Photofrin (2.5 mg per kg of body weight) certainly adds to the sensitivity of photo-detection, but autofluorescence alone also has promising features for detecting premalignant and malignant lesions of the oral mucosa.

摘要

利用体内荧光进行光检测,研究了化学诱导的Wistar大鼠腭黏膜癌前病变和鳞状细胞癌(SCC)的不同阶段。研究发现,通过反复应用致癌物4-硝基喹啉-1-氧化物(4NQO)诱导的大鼠腭上皮发育异常(以大鼠腭上皮异型性指数(EAI)数值表示),其增加幅度与应用期持续时间大致成比例。使用卟吩姆钠诱导的荧光对病变进行光检测,并采用双波长激发和图像相减的方法,试图减少自发荧光。卟吩姆钠剂量为2.5 mg/kg。这是基于该动物模型中光动力疗法(PDT)对正常组织损伤的剂量反应研究,因为其基本原理是研究光检测作为在接受PDT治疗的患者中定位额外(早期)恶性肿瘤的一种方法。结果显示,注射卟吩姆钠后24小时和48小时的荧光强度随4NQO应用时间的延长和EAI的增加而增加。当EAI大于15时,注射和未注射卟吩姆钠所获得的荧光信号之间存在统计学显著差异(p < 0.01)。这些未使用卟吩姆钠的病变的荧光信号(自发荧光)也随着大鼠腭上皮发育异常阶段的增加而增加。然而,使用卟吩姆钠获得的荧光信号总是高于自发荧光信号。从这项研究中,我们得出结论,用卟吩姆钠进行光检测在区分化学诱导的癌前病变和鳞状细胞癌与正常大鼠腭黏膜方面具有潜力。卟吩姆钠(每千克体重2.5 mg)确实提高了光检测的灵敏度,但仅自发荧光在检测口腔黏膜癌前和恶性病变方面也具有良好的特性。

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