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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1985-6-19
pubmed:abstractText
We have developed a brain tumor model in the nude rat utilizing NCI-N417D human small cell carcinoma of the lung grown both intracerebrally and s.c. The median latency period from the time of intracerebral tumor inoculation to the onset of neurological symptoms is 13 days with an intracerebral tumor take rate of 91% (29 of 32). The median survival is 13 days, and all animals were dead by Day 26. The tumor is discrete, well circumscribed, with occasional leptomeningeal spread and with minimal evidence of surrounding cerebral edema. Intracerebrally, this tumor is usually impermeable to Evan's blue:albumin (Mr 68,500) but not fluorescein (Mr 376). Although variable, the intracerebral tumor is less permeable to methotrexate than is the same tumor grown s.c. in the same animal (P less than 0.005). The intraarterial and i.v. routes of methotrexate administration in the presence and absence of blood-brain barrier opening were evaluated. Drug delivery to the intracerebral tumor and ipsilateral brain was significantly (P less than 0.025) greater when the methotrexate was given intraarterially and was significantly (P less than 0.0025) increased after osmotic blood-brain barrier opening. After barrier opening, methotrexate concentration was enhanced 3- to 4-fold in tumor and 10- to 20-fold in brain around tumor. Thus, the nude rat provides a model to investigate the biology and therapeutic responsiveness of human small cell carcinoma of the lung grown intracerebrally where it develops a blood-tumor barrier similar to that seen in humans. This model further provides the unique opportunity to investigate the role of osmotic blood-brain barrier opening in the treatment of a tumor which is sensitive to chemotherapeutic agents and for which tumor-specific monoclonal antibodies are available.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2827-33
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Growth of human lung tumor in the brain of the nude rat as a model to evaluate antitumor agent delivery across the blood-brain barrier.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't