5-aminolaevulinic acid in xenograft tumor models
Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues an...
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creator | Sasaki, Makiko Tanaka, Mamoru Ichikawa, Hiroshi Suzuki, Taketo Nishie, Hirotada Ozeki, Keiji Shimura, Takaya Kubota, Eiji Tanida, Satoshi Kataoka, Hiromi |
description | Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis. |
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Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0249650</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Diagnosis ; Gastrointestinal tumors ; Genetic aspects ; Physiological aspects ; Xenotransplantation</subject><ispartof>PloS one, 2021-04, Vol.16 (4), p.e0249650</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,862,27907,27908</link.rule.ids></links><search><creatorcontrib>Sasaki, Makiko</creatorcontrib><creatorcontrib>Tanaka, Mamoru</creatorcontrib><creatorcontrib>Ichikawa, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Taketo</creatorcontrib><creatorcontrib>Nishie, Hirotada</creatorcontrib><creatorcontrib>Ozeki, Keiji</creatorcontrib><creatorcontrib>Shimura, Takaya</creatorcontrib><creatorcontrib>Kubota, Eiji</creatorcontrib><creatorcontrib>Tanida, Satoshi</creatorcontrib><creatorcontrib>Kataoka, Hiromi</creatorcontrib><title>5-aminolaevulinic acid in xenograft tumor models</title><title>PloS one</title><description>Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.</description><subject>Diagnosis</subject><subject>Gastrointestinal tumors</subject><subject>Genetic aspects</subject><subject>Physiological aspects</subject><subject>Xenotransplantation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNptUE1LxDAUDKLguvoPPBQ8t-a7yXFZ1BUWvOx9eU1eSpY0kbYr_nwLetiDzOENw8xj3iPkkdGGiZY9n8p5zJCaz5KxoVxaregVWTEreK05FdcX_JbcTdOJUiWM1itCVQ1DzCUBfp1TzNFV4KKvYq6-MZd-hDBX83koYzUUj2m6JzcB0oQPf3NNDq8vh-2u3n-8vW83-7rXraqFCSC4XLo4gyAtqC6IwCl6x6T2naSqtcxytNJoWI5ALzgaDMyh75gQa_L0u7aHhMeYQ5lHcEOc3HGjVdtSLYxaXM0_rgUeh-iWb4S46BeBH407V7M</recordid><startdate>20210407</startdate><enddate>20210407</enddate><creator>Sasaki, Makiko</creator><creator>Tanaka, Mamoru</creator><creator>Ichikawa, Hiroshi</creator><creator>Suzuki, Taketo</creator><creator>Nishie, Hirotada</creator><creator>Ozeki, Keiji</creator><creator>Shimura, Takaya</creator><creator>Kubota, Eiji</creator><creator>Tanida, Satoshi</creator><creator>Kataoka, Hiromi</creator><general>Public Library of Science</general><scope/></search><sort><creationdate>20210407</creationdate><title>5-aminolaevulinic acid in xenograft tumor models</title><author>Sasaki, Makiko ; Tanaka, Mamoru ; Ichikawa, Hiroshi ; Suzuki, Taketo ; Nishie, Hirotada ; Ozeki, Keiji ; Shimura, Takaya ; Kubota, Eiji ; Tanida, Satoshi ; Kataoka, Hiromi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g675-38fa324024c8ea49a5bf3f20edc146db40579192e9486a137ed32e8ef1cedb133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Diagnosis</topic><topic>Gastrointestinal tumors</topic><topic>Genetic aspects</topic><topic>Physiological aspects</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sasaki, Makiko</creatorcontrib><creatorcontrib>Tanaka, Mamoru</creatorcontrib><creatorcontrib>Ichikawa, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Taketo</creatorcontrib><creatorcontrib>Nishie, Hirotada</creatorcontrib><creatorcontrib>Ozeki, Keiji</creatorcontrib><creatorcontrib>Shimura, Takaya</creatorcontrib><creatorcontrib>Kubota, Eiji</creatorcontrib><creatorcontrib>Tanida, Satoshi</creatorcontrib><creatorcontrib>Kataoka, Hiromi</creatorcontrib><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sasaki, Makiko</au><au>Tanaka, Mamoru</au><au>Ichikawa, Hiroshi</au><au>Suzuki, Taketo</au><au>Nishie, Hirotada</au><au>Ozeki, Keiji</au><au>Shimura, Takaya</au><au>Kubota, Eiji</au><au>Tanida, Satoshi</au><au>Kataoka, Hiromi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5-aminolaevulinic acid in xenograft tumor models</atitle><jtitle>PloS one</jtitle><date>2021-04-07</date><risdate>2021</risdate><volume>16</volume><issue>4</issue><spage>e0249650</spage><pages>e0249650-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0249650</doi></addata></record> |
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subjects | Diagnosis Gastrointestinal tumors Genetic aspects Physiological aspects Xenotransplantation |
title | 5-aminolaevulinic acid in xenograft tumor models |
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