{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:56:51Z","timestamp":1777528611098,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,1,18]],"date-time":"2010-01-18T00:00:00Z","timestamp":1263772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic lupus erythematosus is a chronic autoimmune disorder that predominantly affects women of childbearing age. Lupus-associated glomerulonephritis is a major cause of mortality in these patients. Current treatment protocols for systemic lupus erythematosus include cyclophosphamide, prednisolone, azathioprine, and mycophenolate mofetil. However, in mice none of these agents alone or in combination were shown to reverse established proteinuria. Using New Zealand Black \u00d7 New Zealand White F1 mice, we report that administration of the topoisomerase I inhibitor irinotecan from week 13 completely prevented the onset of proteinuria and prolonged survival up to at least 90 wk without detectable side effects. Furthermore, application of irinotecan to mice with established lupus nephritis, as indicated by grade 3+ (\u2265300 mg\/dl) and grade 4+ (\u22652000 mg\/dl) proteinuria and, according to a median age of 35 wk, resulted in remission rates of 75% and 55%, respectively. Survival was significantly prolonged with 73 wk (grade 3+ and 4+ combined) versus 40 wk for control animals. Although total IgG and anti-dsDNA Abs in the serum and mesangial IgG deposits in the kidneys were not reduced in irinotecan-treated mice, subendothelial immune deposits were considerably diminished, suggesting a prevention of glomerular basement membrane disruption. This effect was accompanied by increased rates of ssDNA breaks and inhibition of renal cell apoptosis being different to what is known about irinotecan in anticancer therapy. In conclusion, our data provide evidence that irinotecan might represent an entirely new strategy for the treatment of systemic lupus erythematosus.<\/jats:p>","DOI":"10.4049\/jimmunol.0903153","type":"journal-article","created":{"date-parts":[[2010,1,18]],"date-time":"2010-01-18T21:40:27Z","timestamp":1263850827000},"page":"2175-2182","source":"Crossref","is-referenced-by-count":27,"title":["Reversal of Established Lupus Nephritis and Prolonged Survival of New Zealand Black \u00d7 New Zealand White Mice Treated with the Topoisomerase I Inhibitor Irinotecan"],"prefix":"10.1093","volume":"184","author":[{"given":"Manuela","family":"Frese-Schaper","sequence":"first","affiliation":[{"name":"Department of Clinical Research, University Hospital Bern"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Zbaeren","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University Hospital Bern"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Gugger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Bern , Bern,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Monestier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Temple University School of Medicine , Philadelphia, PA 19140"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Frese","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University Hospital Bern"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,1,18]]},"reference":[{"key":"2025032603471742000_r1","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1177\/096120339500400606","article-title":"Prevalence of self-reported physician-diagnosed systemic lupus erythematosus in the USA.","volume":"4","author":"Hochberg","year":"1995","journal-title":"Lupus"},{"key":"2025032603471742000_r2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1681\/ASN.V102413","article-title":"Lupus nephritis.","volume":"10","author":"Cameron","year":"1999","journal-title":"J. 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