{"data":{"id":"10.6084/m9.figshare.c.2032637","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2032637","prefix":"10.6084","suffix":"m9.figshare.c.2032637","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Yano, Shuya","givenName":"Shuya","familyName":"Yano","affiliation":[],"nameIdentifiers":[]},{"name":"Miwa, Shinji","givenName":"Shinji","familyName":"Miwa","affiliation":[],"nameIdentifiers":[]},{"name":"Mii, Sumiyuki","givenName":"Sumiyuki","familyName":"Mii","affiliation":[],"nameIdentifiers":[]},{"name":"Hiroshima, Yukihiko","givenName":"Yukihiko","familyName":"Hiroshima","affiliation":[],"nameIdentifiers":[]},{"name":"Uehara, Fuminaru","givenName":"Fuminaru","familyName":"Uehara","affiliation":[],"nameIdentifiers":[]},{"name":"Kishimoto, Hiroyuki","givenName":"Hiroyuki","familyName":"Kishimoto","affiliation":[],"nameIdentifiers":[]},{"name":"Tazawa, Hiroshi","givenName":"Hiroshi","familyName":"Tazawa","affiliation":[],"nameIdentifiers":[]},{"name":"Zhao, Ming","givenName":"Ming","familyName":"Zhao","affiliation":[],"nameIdentifiers":[]},{"name":"Bouvet, Michael","givenName":"Michael","familyName":"Bouvet","affiliation":[],"nameIdentifiers":[]},{"name":"Fujiwara, Toshiyoshi","givenName":"Toshiyoshi","familyName":"Fujiwara","affiliation":[],"nameIdentifiers":[]},{"name":"M Hoffman, Robert","givenName":"Robert","familyName":"M Hoffman","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Cancer cells mimic \u003ci\u003ein vivo\u003c/i\u003e spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biophysics"},{"subject":"Medicine"},{"subject":"Cell Biology"},{"subject":"Pharmacology"},{"subject":"Biotechnology"},{"subject":"Chemical Sciences not elsewhere classified"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Developmental Biology"},{"subject":"Cancer"},{"subject":"Hematology"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G\u003csub\u003e0\u003c/sub\u003e/G\u003csub\u003e1\u003c/sub\u003e phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G\u003csub\u003e2\u003c/sub\u003e/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and \u003ci\u003ein vivo\u003c/i\u003e tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G\u003csub\u003e0\u003c/sub\u003e/G\u003csub\u003e1\u003c/sub\u003e. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as \u003ci\u003ein vivo\u003c/i\u003e, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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