Linked Life Data

11212276

Source:http://linkedlifedata.com/resource/pubmed/id/11212276

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-2-9
pubmed:abstractText
The cellular response to ionizing radiation is governed by the DNA-damage recognition process but is also modulated by cytoplasmic signal transduction cascades that are part of the cellular stress response. Growth-promoting protein kinase C activity antagonizes irradiation-induced cell death, and, therefore, protein kinase C inhibitors might be potent radiosensitizers. The antiproliferative and radiosensitizing effect of the novel N-benzoylated staurosporine analogue PKC412 was tested in vitro against genetically defined p53-wild type (+/+) and p53-deficient (-/-) murine fibrosarcoma cells and in vivo against radioresistant p53-/- murine fibrosarcoma and human colon adenocarcinoma tumor xenograft (SW480, p53-mutated). PKC412 sensitized both p53+/+ and p53-/- tumor cells in vitro and in vivo for treatment with ionizing radiation but with a different mechanism of radiosensitization depending on the p53 status. In p53+/+, cells combined treatment with PKC412 and ionizing radiation drastically induced apoptotic cell death, whereas no apoptosis induction could be observed in p53-deficient cells in vitro and in histological tumor sections. Combined treatment resulted in an increased G2 cell cycle distribution in p53-/- cells at PKC412 concentrations that did not alter cell cycle distribution when applied alone. In vivo, a minimal treatment regimen during 4 consecutive days of PKC412 (4 x 100 mg/kg) in combination with ionizing radiation (4 x 3 Gy) exerted a substantial tumor growth delay for both p53-disfunctional tumor xenografts and showed that the clinically relevant protein kinase C inhibitor PKC412 is a promising new radiosensitizer with a potentially broad therapeutic window.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
732-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11212276-Animals, pubmed-meshheading:11212276-Antineoplastic Agents, pubmed-meshheading:11212276-Apoptosis, pubmed-meshheading:11212276-Cell Survival, pubmed-meshheading:11212276-Cells, Cultured, pubmed-meshheading:11212276-Combined Modality Therapy, pubmed-meshheading:11212276-Dose-Response Relationship, Drug, pubmed-meshheading:11212276-Dose-Response Relationship, Radiation, pubmed-meshheading:11212276-Enzyme Inhibitors, pubmed-meshheading:11212276-Genotype, pubmed-meshheading:11212276-Humans, pubmed-meshheading:11212276-Mice, pubmed-meshheading:11212276-Mice, Nude, pubmed-meshheading:11212276-Neoplasm Transplantation, pubmed-meshheading:11212276-Neoplasms, Experimental, pubmed-meshheading:11212276-Protein Kinase C, pubmed-meshheading:11212276-Staurosporine, pubmed-meshheading:11212276-Tumor Cells, Cultured, pubmed-meshheading:11212276-Tumor Suppressor Protein p53, pubmed-meshheading:11212276-Xenograft Model Antitumor Assays
pubmed:year
2001
pubmed:articleTitle
Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412.
pubmed:affiliation
Department of Radiation Oncology, University Hospital Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't