Linked Life Data

12606785

Source:http://linkedlifedata.com/resource/pubmed/id/12606785

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-2-27
pubmed:abstractText
We have investigated the sensitivity of the cisplatin-resistant enterohepatic tumor cell lines LS174T/R (human colon adenocarcinoma), WIF-B9/R (rat hepatoma-human fibroblast hybrid), and Hepa 1-6/R (mouse hepatoma) to free and liposome-encapsulated cytostatic bile acid derivatives Bamet-R2 and bamet-UD2. Expression of resistance associated genes was measured by quantitative reverse transcription-polymerase chain reaction or Western blotting. Drug uptake was determined by atomic absorption spectrophotometry. In resistant cells, overexpression of MRP1 and MRP2 was accompanied by reduced accumulation of cisplatin. The expression of MDR1 and GST-P was only enhanced in LS 174T/R. A higher expression of p53 was seen in LS 174T/R and Hepa 1-6/R cell lines but not in WIF-B9/R cells. In wild-type counterparts, uptake and cytostatic ability of Bamets were markedly higher (UD2 > R2) than that of cisplatin. Both effects were further enhanced by liposome formulation. Bamets were able to overcome cisplatin resistance in all cell lines. Cisplatin prolonged the survival time of nude mice in whose livers a Hepa 1-6 tumor had been implanted, but failed to exert a beneficial effect when the tumor was Hepa 1-6/R. In both cases, tissue distribution of cisplatin was: kidney >> liver > tumor. Survival was markedly longer in animals receiving Bamet-UD2, even if the implanted tumor was resistant. The accumulation of Bamet-UD2 in tissues was: liver > tumor > kidney. Liposome formulation further enhanced the beneficial properties of Bamet-UD2. Thus, the amount of drug in the tumor was increased and that in liver and kidney was reduced (tumor > liver > kidney), and life span was prolonged. In conclusion, liposomal Bamet-UD2 may be a useful tool to circumvent resistance to chemotherapy, particularly in tumors of the enterohepatic circuit.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
742-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12606785-Animals, pubmed-meshheading:12606785-Antineoplastic Agents, pubmed-meshheading:12606785-Bile Acids and Salts, pubmed-meshheading:12606785-Cisplatin, pubmed-meshheading:12606785-Disease Models, Animal, pubmed-meshheading:12606785-Drug Carriers, pubmed-meshheading:12606785-Drug Delivery Systems, pubmed-meshheading:12606785-Drug Resistance, Neoplasm, pubmed-meshheading:12606785-Humans, pubmed-meshheading:12606785-Liposomes, pubmed-meshheading:12606785-Mice, pubmed-meshheading:12606785-Mice, Nude, pubmed-meshheading:12606785-Neoplasm Transplantation, pubmed-meshheading:12606785-Neoplasms, Experimental, pubmed-meshheading:12606785-Organoplatinum Compounds, pubmed-meshheading:12606785-Treatment Outcome, pubmed-meshheading:12606785-Tumor Cells, Cultured, pubmed-meshheading:12606785-Ursodeoxycholic Acid
pubmed:year
2003
pubmed:articleTitle
Usefulness of liposomes loaded with cytostatic bile acid derivatives to circumvent chemotherapy resistance of enterohepatic tumors.
pubmed:affiliation
Department of Physiology, University of Salamanca, Salamanca, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't