{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:44:58Z","timestamp":1790372698396,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472759"],"award-info":[{"award-number":["81472759"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81611130086"],"award-info":[{"award-number":["81611130086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872902"],"award-info":[{"award-number":["81872902"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with Non\u2010Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP\u201016) alone and that of MCC using both VP\u201016 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI\u2010LY\u201010 and SU\u2010DHL\u20106, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low\u2010dose VP\u201016 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP\u201016 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy\u2010related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP\u201016 48\u00a0hours\u00a0+\u00a0RAD001 24\u00a0hours is the optimal method for treating NHL.<\/jats:p>","DOI":"10.1002\/cam4.2364","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T08:09:49Z","timestamp":1561018189000},"page":"4688-4698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non\u2010Hodgkin lymphoma"],"prefix":"10.1002","volume":"8","author":[{"given":"Ke","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Qing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai\u2010Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Xiao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Qi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9730-9917","authenticated-orcid":false,"given":"Zhi\u2010Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Jia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat\u2010sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.08.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.08.015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3658"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-629543"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2821"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3136-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0205-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.159160"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000484629"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010018"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2016.12.011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.07.013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3923"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13427"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx268"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)30040-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0344-4"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0024"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx300480q"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1009795"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2017.08.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13033563"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-235655"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2006.06.021"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161845"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.33"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.01.040"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2014.89"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2853"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-498964"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(98)00228-7"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05406-y"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.215"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06556-9"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.27058"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.9331"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaq1564"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.11.16658"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2010.07.005"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.2364","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2364","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.2364","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2364","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T17:45:32Z","timestamp":1692726332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.2364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,20]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/cam4.2364"],"URL":"https:\/\/doi.org\/10.1002\/cam4.2364","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,20]]},"assertion":[{"value":"2019-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}