{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:02:34Z","timestamp":1773273754346,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T00:00:00Z","timestamp":1474934400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The combination of stem cell\u2010based gene therapy with chemotherapy comprises an advantageous strategy that results in a reduction of system toxicity effects and an improvement in the general efficacy of treatment. In the present study, we estimated the efficacy of adipose tissue\u2010derived mesenchymal stem cells (AT\u2010MSCs) expressing cytosine deaminase (CDA) combined with lysomustine chemotherapy in mice bearing late stage Lewis lung carcinoma (LLC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adipose tissue\u2010derived mesenchymal stem cells were transfected with non\u2010insert plasmid construct transiently expressing fused cytosine deaminase\u2010uracil phosphoribosyltransferase protein (CDA\/UPRT) or the same construct fused with Herpes Simplex Virus Type1 tegument protein VP22 (CDA\/UPRT\/VP22). Systemic administration of 5\u2010fluorocytosine (5FC) and lysomustine was implemented after a single intratumoral injection of transfected AT\u2010MSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that direct intratumoral transplantation of AT\u2010MSCs expressing CDA\/UPRT or CDA\/UPRT\/VP22 followed by systemic administration of 5FC resulted in a significant tumor growth inhibition. There was a 56% reduction in tumor volume in mice treated by AT\u2010MSCs\u2010CDA\/UPRT\u2009+\u20095FC or with AT\u2010MSCs\u2010CDA\/UPRT\/VP22\u2009+\u20095FC compared to control animals grafted with lung carcinoma alone. Transplantation of AT\u2010MSCs\u2010CDA\/UPRT\u2009+\u20095FC and AT\u2010MSCs\u2010CDA\/UPRT\/VP22\u2009+\u20095FC prolonged the life span of mice bearing LLC by 27% and 31%, respectively. Co\u2010administration of lysomustine and AT\u2010MSCs\u2010CDA\/UPRT\u2009+\u20095FC led to tumor growth inhibition (by 86%) and life span extension (by 60%) compared to the control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data indicate that a combination CDA\/UPRT\u2010expressing AT\u2010MSCs with lysomustine has a superior antitumor effect in the murine lung carcinoma model compared to monotherapies with transfected AT\u2010MSCs or lysomustine alone, possibly because of a synergistic effect of the combination therapy. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.2894","type":"journal-article","created":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T09:27:35Z","timestamp":1469611655000},"page":"220-233","source":"Crossref","is-referenced-by-count":10,"title":["Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition"],"prefix":"10.1002","volume":"18","author":[{"given":"Lyudmila S.","family":"Krassikova","sequence":"first","affiliation":[{"name":"Pushchino State Institute of Natural Sciences  Pushchino Russia"},{"name":"Engelhardt Institute of Molecular Biology RAS  Moscow Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saida S.","family":"Karshieva","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology RAS  Moscow Russia"},{"name":"N. N. Blokhin Cancer Research Center  Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan B.","family":"Cheglakov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology RAS  Moscow Russia"},{"name":"N. N. 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