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粪卟啉原氧化酶的表达与 5-氨基酮戊酸介导的光动力诊断对上消化道癌的检测有关。

Expression of coproporphyrinogen oxidase is associated with detection of upper gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic diagnosis.

机构信息

Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University, Faculty of Medicine, Yonago, Japan.

出版信息

Photodiagnosis Photodyn Ther. 2017 Sep;19:15-21. doi: 10.1016/j.pdpdt.2017.04.003. Epub 2017 Apr 14.

DOI:10.1016/j.pdpdt.2017.04.003
PMID:28416355
Abstract

BACKGROUND

5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer.

METHODS

Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase.

RESULTS

Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors.

CONCLUSION

Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.

摘要

背景

5-氨基酮戊酸是一种光敏剂原卟啉 IX 的前体,已被用于脑和膀胱肿瘤的光动力诊断,副作用较少。尽管大多数上消化道肿瘤可以在光动力诊断中检测到,但一些含有印戒细胞的肿瘤无法可视化。在这里,我们旨在评估原卟啉 IX 的吸收、激活和周转所涉及的蛋白质是否改变了胃癌中的荧光信号。

方法

使用配备蓝色激光的内窥镜对 20 名患者的 23 个病变进行了 5-氨基酮戊酸介导的光动力诊断,该激光会导致光敏剂原卟啉 IX 发出红色荧光发射。在光动力诊断过程中评估红色荧光信号和强度。通过内镜和/或腹腔镜手术切除病变,对标本进行免疫染色,并评估三磷酸腺苷结合盒亚家族 G 成员 2、寡肽转运蛋白-1 和粪卟啉原氧化酶的表达。

结果

四种情况(17.4%)光动力诊断为阴性。三种光动力诊断阴性病变为印戒细胞癌,只有一种为分化腺癌(肠型)。20 例肠型、光动力诊断阳性病变显示粪卟啉原氧化酶高表达,而印戒细胞癌均为阴性。寡肽转运蛋白-1 免疫反应性在肠型肿瘤中显著更高。三磷酸腺苷结合盒亚家族 G 成员 2 的表达倾向于在腔面肿瘤中高于肠型肿瘤。

结论

5-氨基酮戊酸介导的光动力诊断可很好地检测上消化道肠型肿瘤,但不能检测弥漫型肿瘤,如印戒细胞癌,可能与粪卟啉原氧化酶的表达有关。

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