{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:08:56Z","timestamp":1790780936155,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012051","name":"Lupus Research Alliance","doi-asserted-by":"publisher","award":["6670"],"award-info":[{"award-number":["6670"]}],"id":[{"id":"10.13039\/100012051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli\u20101 and topoisomerase, on lupus nephritis in (NZB \u00d7 NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on inflammatory mediators in human renal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female NZBWF1 mice were treated with vehicle, cyclophosphamide (CYC), CPT (1 mg\/kg or 2 mg\/kg), or TPT (0.03 mg\/kg, 0.1 mg\/kg, or 0. 3 mg\/kg) by intraperitoneal injection twice a week, beginning at the age of 25 weeks (n = 8\u201310 mice per group). Blood and urine were collected for monitoring autoantibodies and proteinuria. Mice were euthanized at 40 weeks, and renal pathology scores were assessed. Human renal endothelial and mesangial cells were treated with CPT or TPT, and cytokine expression was measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      None of the NZBWF1 mice treated with 1 mg\/kg or 2 mg\/kg of CPT or 0.3 mg\/kg of TPT had proteinuria &gt;100 mg\/dl at the age of 40 weeks. One of 8 mice treated with 0.1 mg\/kg of TPT and 1 of 10 mice treated with CYC had proteinuria &gt;300 mg\/dl, whereas 90% of the mice treated with vehicle had proteinuria &gt;300 mg\/dl. Compared to vehicle control, mice treated with 1 mg\/kg or 2 mg\/kg of CPT, 0.1 mg\/kg or 0.3 mg\/kg of TPT, or CYC had significantly prolonged survival, attenuated renal injury, diminished splenomegaly, reduced anti\u2013double\u2010stranded DNA autoantibody levels, and reduced IgG and C3 deposits in the glomeruli (all\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Human renal cells treated with CPT or TPT had reduced expression of Fli\u20101 and decreased monocyte chemotactic protein 1 production following stimulation with interferon\u2010\u03b1 (IFN\u03b1) or IFN\u03b3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that low\u2010dose CPT and TPT could be repurposed to treat lupus nephritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41685","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T22:26:18Z","timestamp":1612909578000},"page":"1478-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Camptothecin and Topotecan, Inhibitors of Transcription Factor Fli\u20101 and Topoisomerase, Markedly Ameliorate Lupus Nephritis in (NZB \u00d7 NZW)F1 Mice and Reduce the Production of Inflammatory Mediators in Human Renal Cells"],"prefix":"10.1002","volume":"73","author":[{"given":"Xuan","family":"Wang","sequence":"first","affiliation":[{"name":"Xiangya Hospital Central South University, Changsha, China, and Medical University of South Carolina  Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim C.","family":"Oates","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina and Ralph H. Johnson VA Medical Center  Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi L.","family":"Helke","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina  Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Gilkeson","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina and Ralph H. 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