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dc.contributor.authorYamaura, Tadayoshien
dc.contributor.authorMiyoshi, Hiroyukien
dc.contributor.authorMaekawa, Hisatsuguen
dc.contributor.authorMorimoto, Tomonorien
dc.contributor.authorYamamoto, Takehitoen
dc.contributor.authorKakizaki, Fumihikoen
dc.contributor.authorHigasa, Koichiroen
dc.contributor.authorKawada, Kenjien
dc.contributor.authorMatsuda, Fumihikoen
dc.contributor.authorSakai, Yoshiharuen
dc.contributor.authorTaketo, M. Marken
dc.contributor.alternative山浦, 忠能ja
dc.contributor.alternative三好, 弘之ja
dc.contributor.alternative前川, 久継ja
dc.contributor.alternative森本, 智紀ja
dc.contributor.alternative山本, 健人ja
dc.contributor.alternative柿崎, 文彦ja
dc.contributor.alternative日笠, 幸一郎ja
dc.contributor.alternative河田, 健二ja
dc.contributor.alternative松田, 文彦ja
dc.contributor.alternative坂井, 義治ja
dc.contributor.alternative武藤, 誠ja
dc.date.accessioned2018-12-27T02:31:40Z-
dc.date.available2018-12-27T02:31:40Z-
dc.date.issued2018-12-25-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/2433/235914-
dc.description.abstractMismatch repair (MMR)-deficient or microsatellite instability (MSI) colorectal cancer includes two subtypes; Lynch syndrome and sporadic MSI cancer, both of which generate multiple neoantigens due to unrepaired mutations. Although such patients respond very well to immune checkpoint therapy, their diagnosis can be confused by low quality DNA samples owing to formalin fixation and/or low cancer cell content. Here we prepared high-quality DNA samples from in vitro-cultured cancer spheroids that consisted of the pure cell population. We evaluated their diagnostic power by on-chip electrophoresis, mutational burden assessment, and direct sequencing. Because formalin-fixed paraffin-embedded (FFPE) tissues are widely used as the DNA source, we compared such samples with spheroid DNA. Additionally, we performed immunohistochemistry (IHC) for MMR proteins on spheroids as well as primary tumor sections. Of 111 cases of colorectal cancer patients, we found seven MSI-high cases in which all diagnostic results agreed on spheroid-based assays, whereas the results with the FFPE DNA were less reliable though analyzable. Importantly, there was an MSS case that appeared as MSI by IHC on primary tumor sections. Based on these results, we propose to employ cultured cancer spheroids as the source of both DNA and IHC specimens for more reliable clinical diagnosis.en
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherImpact Journals, LLCen
dc.rightsYamaura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectcolorectal canceren
dc.subjectspheroiden
dc.subjectcancer stem cellen
dc.subjectmolecular oncologyen
dc.subjectimmunotherapyen
dc.titleAccurate diagnosis of mismatch repair deficiency in colorectal cancer using high-quality DNA samples from cultured stem cellsen
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleOncotargeten
dc.identifier.volume9-
dc.identifier.issue101-
dc.identifier.spage37534-
dc.identifier.epage37548-
dc.relation.doi10.18632/oncotarget.26495-
dc.textversionpublisher-
dc.identifier.pmid30680068-
dcterms.accessRightsopen access-
dc.identifier.eissn1949-2553-
出現コレクション:学術雑誌掲載論文等

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