Linked Life Data

12006511

Source:http://linkedlifedata.com/resource/pubmed/id/12006511

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-5-13
pubmed:abstractText
Colon carcinomas frequently express the epidermal growth factor receptor (EGFR), and this expression correlates with more aggressive disease and poor prognosis. Previous studies have shown that EGFR blockade by monoclonal antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these tumors in athymic mice. In this report, we have studied the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice. IMC-C225 was tested at a dose of 1 or 0.5 mg administered q3d. CPT-11 was administered at a dose of 100 mg/kg/week or a maximum tolerated dose of 150 mg/kg/week. Treatment with the combination of IMC-C225 (1 and 0.5 mg) and CPT-11 (100 mg/kg) significantly inhibited the growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (P < 0.05). Combination therapy with IMC-C225 (1 mg) and the MTD of CPT-11 (150 mg/kg) resulted in a regression rate of 100 and 60% of established DLD-1 and HT-29 tumors, respectively. In a refractory tumor model, combined treatment with IMC-C225 and CPT-11 significantly inhibited the growth of CPT-11 refractory DLD-1 and HT-29 tumors, whereas either agent alone did not control tumor growth. Histological examination of treated tumors showed extensive tumor necrosis, decreased tumor cell proliferation, increased tumor cell apoptosis, and a marked decrease in tumor vasculature. These results suggest that EGFR blockade by IMC-C225 combined with topoisomerase I inhibitors may be an effective therapy against chemorefractory colorectal carcinoma tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
994-1003
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12006511-Animals, pubmed-meshheading:12006511-Antibodies, Monoclonal, pubmed-meshheading:12006511-Antigens, CD31, pubmed-meshheading:12006511-Antineoplastic Agents, Phytogenic, pubmed-meshheading:12006511-Apoptosis, pubmed-meshheading:12006511-Camptothecin, pubmed-meshheading:12006511-Cell Division, pubmed-meshheading:12006511-Colorectal Neoplasms, pubmed-meshheading:12006511-Drug Therapy, Combination, pubmed-meshheading:12006511-Female, pubmed-meshheading:12006511-HT29 Cells, pubmed-meshheading:12006511-Humans, pubmed-meshheading:12006511-Ki-67 Antigen, pubmed-meshheading:12006511-Mice, pubmed-meshheading:12006511-Mice, Nude, pubmed-meshheading:12006511-Neoplasm Transplantation, pubmed-meshheading:12006511-Receptor, Epidermal Growth Factor, pubmed-meshheading:12006511-Time Factors, pubmed-meshheading:12006511-Tumor Cells, Cultured, pubmed-meshheading:12006511-Xenograft Model Antitumor Assays
pubmed:year
2002
pubmed:articleTitle
Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts.
pubmed:affiliation
Department of Immunology, ImClone Systems, Inc., New York, New York 10014, USA.
pubmed:publicationType
Journal Article