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Mouse Models of Gastric Carcinogenesis
Yu, Sungsook,Yang, Mijeong,Nam, Ki Taek The Korean Gastric Cancer Association 2014 Journal of gastric cancer Vol.14 No.2
Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.
Yu, Sungsook,Yang, Mijeong,Lim, Kyung-Min,Cho, Yejin,Kim, Hyunji,Lee, Keunwook,Jeong, Sang-Ho,Coffey, Robert J.,Goldenring, James R.,Nam, Ki Taek Elsevier 2018 The American journal of pathology Vol.188 No.12
<P>Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a transmembrane protein that antagonizes epidermal growth factor receptor signaling in epithelial tissues. LRIG1 is down-regulated in various epithelial cancers, including bladder, breast, and colorectal cancer, suggesting that it functions as a tumor suppressor. However, its role in gastric carcinogenesis is not well understood. Here, we investigated the changes in LRIG1 expression during the stages of gastric cancer. We used a DMP-777–induced spasmolytic polypeptide-expressing metaplasia mouse model and a tissue array of human gastric cancer lesions. The effects of LRIG1 knockdown were also assessed using the human gastric cancer cell line SNU638 in a xenograft model. LRIG1 expression varied over the course of gastric carcinogenesis, increasing in spasmolytic polypeptide-expressing metaplasia lesions but disappearing in intestinal metaplasia and cancer lesions, and the increase was concurrent with the up-regulation of epidermal growth factor receptor. In addition, LRIG1 knockdown promoted the tumorigenic potential <I>in vitro</I>, which was manifested as increased proliferation, invasiveness, and migration as well as increased tumor size <I>in vivo</I> in the xenograft model. Furthermore, LRIG1 expression was determined to be a positive prognostic biomarker for the survival of gastric cancer patients. Collectively, our findings indicate that LRIG1 expression is closely related wto gastric carcinogenesis and may play a vital role as a tumor suppressor through the modulation of epidermal growth factor receptor activity.</P>
Li, Xingshu,Yu, Sungsook,Lee, Yoonji,Guo, Tian,Kwon, Nahyun,Lee, Dayoung,Yeom, Su Cheong,Cho, Yejin,Kim, Gyoungmi,Huang, Jian-Dong,Choi, Sun,Nam, Ki Taek,Yoon, Juyoung American Chemical Society 2019 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.141 No.3
<P>Albumin is a promising candidate as a biomarker for potential disease diagnostics and has been extensively used as a drug delivery carrier for decades. In these two directions, many albumin-detecting probes and exogenous albumin-based nanocomposite delivery systems have been developed. However, there are only a few cases demonstrating the specific interactions of exogenous probes with albumin <I>in vivo</I>, and nanocomposite delivery systems usually suffer from tedious fabrication processes and potential toxicity of the complexes. Herein, we demonstrate a facile “one-for-all” switchable nanotheranostic (NanoPcS) for both albumin detection and cancer treatment. In particular, the <I>in vivo</I> specific binding between albumin and PcS, arising from the disassembly of injected NanoPcS, is confirmed using an inducible transgenic mouse system. Fluorescence imaging and antitumor tests on different tumor models suggest that NanoPcS has superior tumor-targeting ability and the potential for time-modulated, activatable photodynamic therapy.</P> [FIG OMISSION]</BR>