| pubmed-article:11120846 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0023884 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0022801 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0655013 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0021084 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C1456820 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0600688 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:11120846 | lifeskim:mentions | umls-concept:C0750540 | lld:lifeskim |
| pubmed-article:11120846 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:11120846 | pubmed:dateCreated | 2000-12-21 | lld:pubmed |
| pubmed-article:11120846 | pubmed:abstractText | LMB-2 (anti-Tac(Fv)-PE38) is a recombinant immunotoxin composed of the Fv fragment of the anti-Tac Ab fused to a 38-kDa form of Pseudomonas: exotoxin A. Recent clinical trials showed that LMB-2 is a promising agent for the treatment of patients with Tac-positive leukemia or lymphoma. One major side effect that needs to be overcome is nonspecific liver toxicity. In the current study, we have analyzed the mechanism of this toxicity using a mouse model. Mice that were injected with a lethal dose of LMB-2 showed severe hepatic necrosis. Immunohistochemistry revealed that LMB-2 accumulated in Kupffer cells in the liver, suggesting that the damage to the hepatocytes was indirect. When we examined the effects of LMB-2 on peritoneal macrophages, cells in the same lineage as Kupffer cells, we found that LMB-2 induced the production of TNF-alpha by these cells. Following LMB-2 administration to mice, the levels of TNF-alpha in the liver increased to very high levels, whereas the rise in serum levels was modest. In addition, the LMB-2-induced liver toxicity was blocked by a specific TNF binding protein (TNFsRp55). Liver toxicity was also blocked by indomethacin, which also blocked the rise of TNF-alpha in the liver. Both TNFsRp55 and indomethacin treatment protected mice against a lethal dose of LMB-2. These data indicate that TNF-alpha produced in the liver by Kupffer cells has an important causal role in the nonspecific liver toxicity of LMB-2. These findings have important clinical implications for the use of immunotoxins in the therapy of patients with cancer. | lld:pubmed |
| pubmed-article:11120846 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11120846 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11120846 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11120846 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11120846 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:11120846 | pubmed:issn | 0022-1767 | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:PastanII | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:NagataSS | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:WillinghamMM | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:TsutsumiYY | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:PECKB JBJ | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:WangQ CQC | lld:pubmed |
| pubmed-article:11120846 | pubmed:author | pubmed-author:KreitmanR JRJ | lld:pubmed |
| pubmed-article:11120846 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11120846 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:11120846 | pubmed:volume | 165 | lld:pubmed |
| pubmed-article:11120846 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11120846 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11120846 | pubmed:pagination | 7150-6 | lld:pubmed |
| pubmed-article:11120846 | pubmed:dateRevised | 2004-11-17 | lld:pubmed |
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| pubmed-article:11120846 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:11120846 | pubmed:articleTitle | Inhibition of TNF-alpha produced by Kupffer cells protects against the nonspecific liver toxicity of immunotoxin anti-Tac(Fv)-PE38, LMB-2. | lld:pubmed |
| pubmed-article:11120846 | pubmed:affiliation | Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. | lld:pubmed |
| pubmed-article:11120846 | pubmed:publicationType | Journal Article | lld:pubmed |
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