Linked Life Data

10415871

Source:http://linkedlifedata.com/resource/pubmed/id/10415871

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-8-19
pubmed:abstractText
The survival rate for patients with pancreatic ductal adenocarcinoma (PDAC) is among the poorest for all cancers. The factors that contribute to this poor prognosis are lack of effective early detection, high rate of metastases and a generally refractory response to available treatment modalities. The most commonly used treatment methods--chemotherapy and radiation therapy--are mainly used for symptom palliation, with surgery being the only "curative" treatment option. The use of combinations of treatment modalities is the only therapy available to patients with locally advanced disease or that which is surgically unresectable. These options are still not sufficient to increase patient survival time significantly. The aggressive behavior and poor prognosis of this cancer is associated with an increased expression of many growth factors and their cognate receptors. We have demonstrated previously the aberrant expression of the Trk receptors (Trks A, B, and C) in PDAC specimens and human PDAC-derived cell lines and a biphasic, dose-dependent response of specific neurotrophic agents on the in vitro invasiveness of PDAC cells. Based on these data we have evaluated the therapeutic potential of inhibiting neurotrophin-Trk interactions using a selective Trk tyrosine kinase inhibitor (CEP-701) on subcutaneous (s.c.) and tracheal xenografts derived from the poorly differentiated PDAC cell line, Panc1. We demonstrate that CEP-701 administration at 10 mg/kg s.c. BID for 21 days inhibited tumor growth of the Panc1 s.c. xenografts in a statistically-significant manner (p < 0.01) compared to vehicle controls, in the absence of morbidity and mortality. A T/C value of 25% was observed for CEP-701-treated s.c. xenografts. In addition, CEP-701 administration inhibited tumor cell invasion in the s.c. tracheal xenograft model of in vivo invasiveness. Taken together, these data suggest that further studies are warranted to evaluate CEP-701 as a potential therapeutic agent in the treatment of PDAC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
880
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
252-62
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10415871-Adenocarcinoma, pubmed-meshheading:10415871-Animals, pubmed-meshheading:10415871-Antineoplastic Agents, pubmed-meshheading:10415871-Carbazoles, pubmed-meshheading:10415871-Enzyme Inhibitors, pubmed-meshheading:10415871-Female, pubmed-meshheading:10415871-Humans, pubmed-meshheading:10415871-Indoles, pubmed-meshheading:10415871-Injections, Subcutaneous, pubmed-meshheading:10415871-Mice, pubmed-meshheading:10415871-Mice, Inbred BALB C, pubmed-meshheading:10415871-Mice, Nude, pubmed-meshheading:10415871-Molecular Structure, pubmed-meshheading:10415871-Neoplasm Invasiveness, pubmed-meshheading:10415871-Neoplasm Transplantation, pubmed-meshheading:10415871-Pancreatic Neoplasms, pubmed-meshheading:10415871-Rats, pubmed-meshheading:10415871-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:10415871-Trachea
pubmed:year
1999
pubmed:articleTitle
The novel Trk receptor tyrosine kinase inhibitor CEP-701 (KT-5555) exhibits antitumor efficacy against human pancreatic carcinoma (Panc1) xenograft growth and in vivo invasiveness.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania, USA.
pubmed:publicationType
Journal Article