{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:03:17Z","timestamp":1777482197865,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Biotherapy and Radiopharmaceuticals"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      The cross-reacting material 197 (CRM197) is a mutation of the diphtheria toxin. The protein of CRM197 was used successfully for the therapy of various tumors in the recent studies. In this study, the recombinant adenoviruses containing the\n                      <jats:italic toggle=\"yes\">CRM197<\/jats:italic>\n                      gene(AdCRM197) were used to enhance the cellar toxicity of gemcitabine in human glioma U87, U251, and H4 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures:<\/jats:title>\n                    <jats:p>\n                      MTT assay and flow cytometric analysis were performed to test the apoptosis of the U87, U251 and H4 cells with the combined treatment of AdCRM197 plus gemcitabine. Western blotting analyses were carried out to detect the cell apoptosis of the mitochondrial pathway. And the xenograft nude mice were used to observe the enhanced antitumor effect of AdCRM197\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      AdCRM197 sensitizes human glioma cells to gemcitabine\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      by the mitochondrial pathway. Tumor volume was inhibited and survival time was prolonged in the U251 or U87 xenografted nude mice with gemcitabine plus AdCRM197. The enhanced antitumor effect of AdCRM197 was also detected by the immunohistochemical analyses and TUNEL staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The authors found that AdCRM197 sensitized the human glioma to gemcitabine not only\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      but also\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . They provide the first evidence that adenovirus-mediated CRM197 may be a potential chemosensitizing agent for the treatment of cancer. The diphtheria toxin is of great toxicity that even one molecule of diphtheria toxin is enough to kill one cell. However, because of the high toxicity, the diphtheria toxin would kill the packing cells when it is being packaged into the recombinant viruses. Therefore, the diphtheria toxin is hard to be used in the gene therapy for virus vectors. The cross-reacting material 197 (CRM197) is a mutation of the diphtheria toxin. Unlike DTA, CRM197 exhibit a weak toxicity. The week toxicity of CRM197 is a good feature for the virus packaging. In the present study, we used a recombinant adenovirus which carried a\n                      <jats:italic toggle=\"yes\">CRM197<\/jats:italic>\n                      gene (AdCRM197) to enhance the cellar toxicity of gemcitabine in human glioma cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/cbr.2017.2363","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T11:25:56Z","timestamp":1545823556000},"page":"171-180","source":"Crossref","is-referenced-by-count":2,"title":["Adenovirus-Mediated CRM197 Sensitizes Human Glioma Cells to Gemcitabine by the Mitochondrial Pathway"],"prefix":"10.1177","volume":"34","author":[{"given":"Lv-Xia","family":"Dai","sequence":"first","affiliation":[{"name":"Sichuan University","place":["China"]},{"name":"Chengdu Medical College","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubei University of Medicine","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Min","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sizhou","family":"Huang","sequence":"additional","affiliation":[{"name":"Chengdu Medical College","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chengdu Medical College","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-Yi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Cao","sequence":"additional","affiliation":[{"name":"Chengdu Medical College","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nos218"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou223"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70105-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.22.6853"},{"key":"e_1_3_4_6_2","first-page":"4660","article-title":"Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: Possible strategy for inducing cancer cell suicide","volume":"46","author":"Maxwell IH","year":"1986","unstructured":"Maxwell IH, , Maxwell F, , Glode LM. 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Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute lymphoblastic leukemia. Anticancer Res, 2011; 31:2483.","journal-title":"Anticancer Res"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24031"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.05.052"},{"key":"e_1_3_4_20_2","first-page":"2461","article-title":"A possible clinical adaptation of CRM197 in combination with conventional chemotherapeutic agents for ovarian cancer","volume":"31","author":"Tsujioka H","year":"2011","unstructured":"Tsujioka H, , Fukami T, , Yotsumoto F, et al. A possible clinical adaptation of CRM197 in combination with conventional chemotherapeutic agents for ovarian cancer. 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