Linked Life Data

9816179

Source:http://linkedlifedata.com/resource/pubmed/id/9816179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-10
pubmed:abstractText
The relationship between tumor physiology and the pharmacokinetics of 2',2' difluorodeoxycytidine [gemcitabine (dFdC)] in ex vivo perfused human small cell lung cancer was examined. Two small cell lung cancer sublines, 54A and 54B, with known in vivo sensitivity to dFdC, were grown as tissue-isolated tumors in athymic mice and perfused ex vivo with or without 20-40 micrometer dFdC. Arteriovenous differences in gases, pH, and metabolites were determined before and during drug infusion. The geometric flow resistance (FR) of individual tumors was calculated, and dFdC and its inactive metabolite 2',2' difluorodeoxyuridine were determined by high-performance liquid chromatography of consecutive samples from the output line. Both tumors had prominent lactate production concurrent with a significant O2 consumption. The arteriovenous pH drop was approximately 0.3 in both tumor lines. Significant metabolic differences between 54A and 54B tumors were found that elucidated previously described differences further. Pharmacokinetic analysis showed that the initial tumor uptake of dFdC was flow limited, and a significant inverse correlation between the geometric FR and initial drug uptake was found. The rate constant for recovery of the drug in the tumor outflow was greater in 54B tumors (P < 0.05), and the geometric FR was greater in 54A tumors (P < 0.01). The drug conversion rate was independent of physiological parameters. Attempts to modify the delivery of dFdC should be directed at the tumor blood flow distribution. More generally, our experimental model provides useful new insight into metabolism and intratumor pharmacokinetics of chemotherapeutic agents in solid tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
359-67
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Intratumor pharmacokinetics, flow resistance, and metabolism during gemcitabine infusion in ex vivo perfused human small cell lung cancer.
pubmed:affiliation
Edwin L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't