Linked Life Data

15205332

Source:http://linkedlifedata.com/resource/pubmed/id/15205332

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-6-18
pubmed:abstractText
Once prostate cancer metastasizes to bone, conventional chemotherapy is largely ineffective. We hypothesized that inhibition of phosphorylation of the epidermal growth factor receptor (EGF-R) and platelet-derived growth factor receptor (PDGF-R) expressed on tumor cells and tumor-associated endothelial cells, which is associated with tumor progression, in combination with paclitaxel would inhibit experimental prostate cancer bone metastasis and preserve bone structure. We tested this hypothesis in nude mice, using human PC-3MM2 prostate cancer cells. PC-3MM2 cells growing adjacent to bone tissue and endothelial cells within these lesions expressed phosphorylated EGF-R and PDGF-R alpha and -beta on their surfaces. The percentage of positive endothelial cells and the intensity of receptor expression directly correlated with proximity to bone tissue. Oral administration of PKI166 inhibited the phosphorylation of EGF-R but not PDGF-R, whereas oral administration of STI571 inhibited the phosphorylation of PDGF-R but not EGF-R. Combination therapy using oral PKI166 and STI571 with i.p. injections of paclitaxel induced a high level of apoptosis in tumor vascular endothelial cells and tumor cells in parallel with inhibition of tumor growth in the bone, preservation of bone structure, and reduction of lymph node metastasis. Collectively, these data demonstrate that blockade of phosphorylation of EGF-R and PDGF-R coupled with administration of paclitaxel significantly suppresses experimental human prostate cancer bone metastasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4201-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15205332-Animals, pubmed-meshheading:15205332-Antigens, CD31, pubmed-meshheading:15205332-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:15205332-Apoptosis, pubmed-meshheading:15205332-Bone Neoplasms, pubmed-meshheading:15205332-Cell Division, pubmed-meshheading:15205332-Enzyme Inhibitors, pubmed-meshheading:15205332-Humans, pubmed-meshheading:15205332-In Situ Nick-End Labeling, pubmed-meshheading:15205332-Male, pubmed-meshheading:15205332-Mice, pubmed-meshheading:15205332-Mice, Nude, pubmed-meshheading:15205332-Paclitaxel, pubmed-meshheading:15205332-Phosphorylation, pubmed-meshheading:15205332-Piperazines, pubmed-meshheading:15205332-Prostatic Neoplasms, pubmed-meshheading:15205332-Pyrimidines, pubmed-meshheading:15205332-Pyrroles, pubmed-meshheading:15205332-Receptor, Epidermal Growth Factor, pubmed-meshheading:15205332-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:15205332-Substrate Specificity, pubmed-meshheading:15205332-Xenograft Model Antitumor Assays
pubmed:year
2004
pubmed:articleTitle
Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice.
pubmed:affiliation
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.