Linked Life Data

17018587

Source:http://linkedlifedata.com/resource/pubmed/id/17018587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2006-10-4
pubmed:abstractText
Inactivation of p53 function, which frequently occurs in tumors, can significantly modulate tumor cell sensitivity to radiation and chemotherapeutic drugs. However, in addition to acting on malignant cells, anticancer agents act on the cells of tumor stroma, causing activation of a p53 response. The effect of this response on treatment outcome has been the subject of the present study. Tumors with p53-deficient stroma were generated using mouse tumorigenic packaging cells that produce a p53 inhibitory retrovirus, encoding a dominant-negative p53 mutant. Tumors maintaining wild-type p53 in their stroma were formed by cells of similar origin but deficient in retroviral production due to the deletion of the packaging signal in the retroviral vector. Comparison of these tumor models, differing only in p53 status of their stromas, showed that tumors with p53-deficient stroma were significantly more sensitive to experimental chemotherapy and radiotherapy. A similar effect was achieved when anticancer treatment was combined with pharmacologic suppression of p53 by the cyclic form of pifithrin alpha, a small-molecule inhibitor of p53. Potentiation of the anticancer effect of chemotherapy and radiotherapy by p53 suppression in the tumor stroma is likely to be due to the increased sensitivity of p53-deficient endothelium to genotoxic stress as shown both in cell culture and in experimental tumors. Thus, reversible pharmacologic suppression of p53 may be a viable approach to improving anticancer treatment via an enhanced antiangiogenic effect of chemotherapy and radiotherapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9356-61
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17018587-Angiogenesis Inhibitors, pubmed-meshheading:17018587-Animals, pubmed-meshheading:17018587-Antineoplastic Agents, Alkylating, pubmed-meshheading:17018587-Benzothiazoles, pubmed-meshheading:17018587-Carcinoma, Lewis Lung, pubmed-meshheading:17018587-Cell Line, Transformed, pubmed-meshheading:17018587-Cyclophosphamide, pubmed-meshheading:17018587-Drug Resistance, Neoplasm, pubmed-meshheading:17018587-Drug Screening Assays, Antitumor, pubmed-meshheading:17018587-Endothelial Cells, pubmed-meshheading:17018587-Fibroblasts, pubmed-meshheading:17018587-Imidazoles, pubmed-meshheading:17018587-Mice, pubmed-meshheading:17018587-Mice, Inbred C57BL, pubmed-meshheading:17018587-NIH 3T3 Cells, pubmed-meshheading:17018587-Protein Conformation, pubmed-meshheading:17018587-Radiation-Sensitizing Agents, pubmed-meshheading:17018587-Rats, pubmed-meshheading:17018587-Stromal Cells, pubmed-meshheading:17018587-Thiazoles, pubmed-meshheading:17018587-Toluene, pubmed-meshheading:17018587-Transduction, Genetic, pubmed-meshheading:17018587-Tumor Suppressor Protein p53
pubmed:year
2006
pubmed:articleTitle
Inhibition of p53 response in tumor stroma improves efficacy of anticancer treatment by increasing antiangiogenic effects of chemotherapy and radiotherapy in mice.
pubmed:affiliation
Department of Molecular Genetics, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural