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Supernatant harvested from Neuro\u20102a cells transfected with the murine FasL cDNA contains FasL and transduces a potent apoptotic signal to Yac\u20101 cells <jats:italic>in vitro<\/jats:italic>. Specificity of FasL\u2010mediated cytotoxicity was confirmed by competition assays using soluble Fas or anti\u2010Fas\/APO\u20101 F(ab')<jats:sub>2<\/jats:sub> fragments which specifically interfere with FasL\u2010Fas\/APO\u20101 interactions. Intraperitoneal injection of FasL\u2010containing supernatant efficiently killed Yac\u20101 target cells which had been implanted in capsules into the peritoneal cavity of mice. Analysis of the target cells revealed DNA fragmentation and nuclear changes typical of apoptosis. As previously shown, intraperitoneal injection of anti\u2010Fas\/APO\u20101 antibodies caused liver failure (Ogasawara, J., Watanabe, F. R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T. and Nagata, S., <jats:italic>Nature<\/jats:italic> 1993. <jats:italic>364<\/jats:italic>: 806) and was observed at doses which did not reduce Yac\u20101 cell viability. In contrast, FasL did not induce histopathology in the liver when applied intraperitoneally at doses cytotoxic for Yac\u20101 cells. However, intravenous administration of FasL induced lethal liver hemorrhages and hepatocyte apoptosis. Thus, locally applied FasL kills tumor cells very efficiently without systemic toxicity and may therefore represent a candidate for local tumor treatment.<\/jats:p>","DOI":"10.1002\/eji.1830250821","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T01:17:47Z","timestamp":1172798267000},"page":"2253-2258","source":"Crossref","is-referenced-by-count":163,"title":["Local Fas\/APO\u20101 (CD95) ligand\u2010mediated tumor cell killing <i>in vivo<\/i>"],"prefix":"10.1002","volume":"25","author":[{"given":"Anne","family":"Rensing\u2010Ehl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Frei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Flury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Matiba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara M.","family":"Mariani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Weller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Aebischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Krammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1972.33"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)62312-8"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90214-6"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90614-5"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"10 709","DOI":"10.1016\/S0021-9258(19)50076-X","volume":"267","author":"Oehm A.","year":"1992","journal-title":"J. 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