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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2A
pubmed:dateCreated
1994-7-25
pubmed:abstractText
The fact that tumors require polyamines for growth has been demonstrated in vitro and in vivo and widely reported. This finding led to the use of polyamine biosynthetic enzymes as targets for antitumor drug design. Highly efficient in vitro selective inhibitors of ornithine decarboxylase such as DFMO do not produce important antitumoral effects in vivo, due to the ability of tumor cells to uptake extracellular polyamines. A new strategy was developed, combining a systematic blockade of all endogenous and exogenous sources of polyamines in vivo. Sources of exogenous polyamines were eliminated by administration of a polyamine-free diet to the animals and decontamination of their gastrointestinal tract. Important antitumoral effects were obtained with this polyamine deprivation and are presented with two experimental models of tumors (Lewis lung carcinoma, Mat Lylu prostatic carcinoma). Biological parameters, modified in cases of cancer, were restored to normal values in treated animals: blood counts and NK cytotoxic activity. Number of metastases was significantly reduced. Given that in man cancer treatment remains unsatisfactory due to incomplete cell kill, development of resistance to treatment and secondary effects of chemotherapy, we chose to investigate the potential interest of polyamine deprivation in this field. By combining clinically applied cytotoxic drugs with polyamine deprivation, we observed an improvement of their antitumoral efficiency: a considerable retardation of tumor growth paired with a marked increase in life-span of the treated animals. Our observations confirm that polyamines absorbed from exogenous sources, mainly food and gastrointestinal tract, play an important role in tumor growth control. Furthermore, the study shows that polyamine deprivation represents an important potential therapeutic tool in improved management of cancer treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
443-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8017845-Animals, pubmed-meshheading:8017845-Cell Division, pubmed-meshheading:8017845-Cyclophosphamide, pubmed-meshheading:8017845-Cytotoxicity, Immunologic, pubmed-meshheading:8017845-Diet, pubmed-meshheading:8017845-Dose-Response Relationship, Drug, pubmed-meshheading:8017845-Hydrolases, pubmed-meshheading:8017845-Kidney, pubmed-meshheading:8017845-Killer Cells, Natural, pubmed-meshheading:8017845-Liver, pubmed-meshheading:8017845-Lung Neoplasms, pubmed-meshheading:8017845-Male, pubmed-meshheading:8017845-Mice, pubmed-meshheading:8017845-Mice, Inbred C57BL, pubmed-meshheading:8017845-Mice, Inbred DBA, pubmed-meshheading:8017845-Polyamines, pubmed-meshheading:8017845-Prostatic Neoplasms, pubmed-meshheading:8017845-Rats, pubmed-meshheading:8017845-Rats, Inbred Strains, pubmed-meshheading:8017845-Spleen
pubmed:articleTitle
Polyamine deprivation: a new tool in cancer treatment.
pubmed:affiliation
Laboratoire de Biologie Cellulaire, Centre Hospitalier-Universitaire de Rennes, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't