MP69-01 ESTABLISHMENT OF A NOVEL ANIMAL MODEL IN CARCINOGENESIS OF UPPER TRACT UROTHELIAL CARCINOMA AND ITS GENE PROFILE

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP69-01 ESTABLISHMENT OF A NOVEL ANIMAL MODEL IN CARCINOGENESIS OF UPPER TRACT UROTHELIAL CARCINOMA AND ITS GENE PROFILE Akinaru Yamamoto, Atsunari Kawashima, Kentaro Jingushi, Yuichi Motoyama, Satoshi Nojima, Sassi Nesrine, Yohei Okuda, Toshiki Oka, Toshihiro Uemura, Gaku Yamamichi, Eisuke Tomiyama, Kosuke Nakano, Makoto Matsushita, Yu Ishizuya, Yoshiyuki Yamamoto, Taigo Kato, Koji Hatano, Tsujikawa Kazutake, and Norio Nonomura Akinaru YamamotoAkinaru Yamamoto More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Kentaro JingushiKentaro Jingushi More articles by this author , Yuichi MotoyamaYuichi Motoyama More articles by this author , Satoshi NojimaSatoshi Nojima More articles by this author , Sassi NesrineSassi Nesrine More articles by this author , Yohei OkudaYohei Okuda More articles by this author , Toshiki OkaToshiki Oka More articles by this author , Toshihiro UemuraToshihiro Uemura More articles by this author , Gaku YamamichiGaku Yamamichi More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Kosuke NakanoKosuke Nakano More articles by this author , Makoto MatsushitaMakoto Matsushita More articles by this author , Yu IshizuyaYu Ishizuya More articles by this author , Yoshiyuki YamamotoYoshiyuki Yamamoto More articles by this author , Taigo KatoTaigo Kato More articles by this author , Koji HatanoKoji Hatano More articles by this author , Tsujikawa KazutakeTsujikawa Kazutake More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper urinary tract (UT) and bladder are known to differ from the embryology stage. There have been numerous reports of mouse models of bladder carcinogenesis, but there are few reports of mouse models of upper tract urothelial carcinogenesis. The aim of this study is to establish a novel mouse model of upper tract urothelial carcinogenesis. METHODS: We used two strains including C57/BL6 of male and female mice. We fed 0.05% N-butyl-N-(4-hydro-oxybutyl) nitorosamine (BBN) from 6 weeks old to the harvest day. The harvested organs were diagnosed by two different pathologists with histopathological evaluation using Hematoxylin and Eosin staining. Both sides of UT from mouse drinking BBN were subjected to whole transcriptome sequencing (WTS). In human samples, 74 upper tract urothelial carcinoma (UTUC) tissues and 73 adjacent normal (AN) tissues also subjected to WTS from 74 UTUC patients. RESULTS: Female mice of certain strain showed early weight loss compared to the others. They showed high incidence of UTUC with less incidence of bladder cancer (Figure 1), while the others rarely had UTUC. The total incidence of UTUC in this mouse strain was 83.3%, with the earliest UTUC observed at 8 weeks after the start of BBN drinking. The incidence of bilateral UTUC was 22.2%, and these individuals showed weight loss relatively early after the start of BBN drinking. The cancerous side of UT expressed a basal type of mRNA expression profile, with increased expression of Cd44, Cdh3, and Krt14, similar to previous reports of bladder carcinogenesis mouse model (Figure 2). We detected 593 differential expressed genes between cancerous side and non-cancerous side of UT in this mouse model, which could also classify human UTUC and AN samples. In pathway enrichment analysis of these genes, several pathways associated with DNA replication were commonly upregulated in cancer tissues between mouse and human samples. CONCLUSIONS: We have established the novel animal model developing UTUC with high probability. This model could reflect the human UTUC. Source of Funding: This work was supported by a KAKENHI grant (21K20968, 22K09523) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e963 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akinaru Yamamoto More articles by this author Atsunari Kawashima More articles by this author Kentaro Jingushi More articles by this author Yuichi Motoyama More articles by this author Satoshi Nojima More articles by this author Sassi Nesrine More articles by this author Yohei Okuda More articles by this author Toshiki Oka More articles by this author Toshihiro Uemura More articles by this author Gaku Yamamichi More articles by this author Eisuke Tomiyama More articles by this author Kosuke Nakano More articles by this author Makoto Matsushita More articles by this author Yu Ishizuya More articles by this author Yoshiyuki Yamamoto More articles by this author Taigo Kato More articles by this author Koji Hatano More articles by this author Tsujikawa Kazutake More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...