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Targeting fructose metabolism by glucose transporter 5 regulation in human cholangiocarcinoma

Genes & Diseases 2022年第6期9卷 1727-1741页

作者： Nattawan Suwannakul Napat Armartmuntree Raynoo Thanan Kaoru Midorikawa Tetsuo Kon Shinji Oikawa Hatasu Kobayashi Ning Ma Shosuke Kawanishi mariko murata Department of Environmental and Molecular Medicine Mie University Graduate School of MedicineTsuMie 514-8507Japan Department of Biochemistry Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Laboratory of Functional Genomics Graduate School of BioscienceNagahama Institute of Bioscience and TechnologyNagahamaShiga 526-0829Japan Graduate School of Health Science Suzuka University of Medical ScienceSuzukaMie 513-8670Japan Faculty of Pharmaceutical Sciences Suzuka University of Medical ScienceSuzukaMie 513-8670Japan

Alterations in cellular metabolism may contribute to tumor proliferation and *** of the facilitative glucose transporter(GLUT)plays a key role in promoting ***5 mediates modulation of fructose utilization,and its overexpression has been associated with poor prognosis in several ***,its metabolic regulation remains poorly ***,we demonstrated elevated GLUT5 expression in human cholangiocarcinoma(CCA),using RNA sequencing data from samples of human tissues and cell lines,as compared to normal liver tissues or a cholangiocyte cell *** exhibiting highexpression of GLUT5 showed increased rates of cell proliferation and ATP production,particularly in a fructose-supplemented *** contrast,GLUT5 silencing attenuated cell proliferation,ATP production,cell migration/invasion,and improved epithelialemesenchymal transition(EMT)***,fructose consumption increased tumor growth in a nude mouse xenograft model,and GLUT5 silencing suppressed growth,supporting the tumor-inhibitory effect of GLUT5 ***,in the metabolic pathways of fructolysis-Warburg effect,the expression levels of relative downstream genes,including ketohexokinase(KHK),aldolase B(ALDOB),lactate dehydrogenase A(LDHA),and monocarboxylate transporter 4(MCT4),as well as hypoxia-inducible factor 1 alpha(HIF1A),were altered in a GLUT5 expression-dependent *** together,these findings indicate that GLUT5 could be a potential target for CCA therapeutic approach via metabolic regulation.

关键词： Cholangiocarcinoma Fructose Glucose transporter 5 Metabolic regulation Warburg effect

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Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion

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World Journal of Gastroenterology 2005年第30期11卷 4644-4649页

作者： Somchai Pinlaor Banchob Sripa Ning Ma Yusuke Hiraku Puangrat Yongvanit Sopit Wongkham Chawalit Pairojkul Vajarabhongsa Bhudhisawasdi Shinji Oikawa mariko murata Reiji Semba Shosuke Kawanishi Department of Parasitology Department of Pathology Department of Anatomy Department of Environmental and Molecular Medicine Department of Biochemistry Department of Surgery

AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.

关键词： 8-Nitroguanine 8-Oxo-7,8-dihydro-2'-deoxyguanosine Hypoxia-inducible factor-1α Cholangiocarcinoma Tumor invasion

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鼻咽癌患者血清和鼻咽组织中8-羟基脱氧鸟苷含量的变化

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中国病理生理杂志 2009年第10期25卷 2047-2049页

作者：黄元姣张贝贝马宁玄超盛晓晓木村真理子广西医科大学医学科学实验中心广西南宁530021 铃鹿医疗科学大学保健卫生学部三重大学医学部环境与分子医学

目的:8-羟基脱氧鸟苷(8-OHdG)是DNA损伤性生物标志物。通过检测鼻咽癌患者血清和鼻咽组织中8-OHdG的水平,初步探究鼻咽癌的发生和发展是否与DNA损伤有关。方法:利用抗8-OHdG单克隆抗体,通过ELISA和免疫荧光组织化学方法分别检测鼻咽癌... 详细信息

目的:8-羟基脱氧鸟苷(8-OHdG)是DNA损伤性生物标志物。通过检测鼻咽癌患者血清和鼻咽组织中8-OHdG的水平,初步探究鼻咽癌的发生和发展是否与DNA损伤有关。方法:利用抗8-OHdG单克隆抗体,通过ELISA和免疫荧光组织化学方法分别检测鼻咽癌患者血清和鼻咽组织中8-OHdG的水平。结果:8-OHdG在鼻咽癌患者血清和组织中表达水平较高,与正常人血清和慢性咽炎组织比较差异显著(P<0.05)。结论:结果提示鼻咽癌的发生和发展可能与8-OHdG的水平有关。8-OHdG有望成为辅助鼻咽癌诊断的一个生物标志物。

关键词：鼻咽肿瘤 8-羟基脱氧鸟苷

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Difficult Intubation in a Patient with Dysphagia after Posterior Occipitocervical Fusion: A Case Report

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Open Journal of Anesthesiology 2017年第5期7卷 121-129页

作者： Junichi Nishiyama Aki Ando Tomohiko murata mariko Watanabe Hajime Yamazaki Satoru Saito Toshiyasu Suzuki Department of Anesthesiology Tokai University School of Medicine Isehara Japan

The authors encountered a case involving difficult intubation during anesthesia for revision of cervical fixation angle in a 62-year-old woman, with a history of chronic rheumatoid arthritis, who experienced dysphagia after initial posterior occipitocervical fusion to correct atlantoaxial subluxation. Two days after initial surgery, she developed trismus with neck flexion and dysphagia, and underwent revision surgery. General anesthesia was planned;however, tracheal intubation using the McGrath laryngoscope and bronchofiberscope was difficult, which prolonged anesthesia induction. Narrowing of the oral and pharyngeal cavities associated with overcorrection of the cervical spine was believed to be the reason for difficulty in manipulating the tracheal intubation devices. In posterior occipitocervical fusion, intraoperative evaluation of the occipito-second cervical vertebra (O-C2) angle is reported to be useful in preventing postoperative dyspnea and/or dysphagia, and avoids the need for revision of fixation angle. However, when revision surgery is needed, selection of airway management methods and tracheal intubation devices are important considerations because patients are likely to have restricted mobility in the cervical spine and narrowing of the oral and pharyngeal cavities.

关键词： Occipitocervical Fusion Postoperative Dysphagia Difficult Intubation O-C2 Angle

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