Document Detail


Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells.
MedLine Citation:
PMID:  16435154     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies. Although multidisciplinary treatments have been introduced, patients with this disease rarely survive longer than 1 year. These findings prompted us to investigate the antitumor activity of molecular targeting agents in thyroid cancer cells.
METHODS: Two tyrosine kinase inhibitors, gefitinib and imatinib, were tested in a poorly differentiated thyroid cancer cell line, KTC-1, and two ATC cell lines, KTC-2 and KTC-3.
RESULTS: All cell lines expressed not only a target molecule of gefitinib, HER1, but also a cognate receptor, HER2. They also expressed target molecules of imatinib, c-ABL and platelet-derived growth factor receptors at various levels. Both agents had modest antitumor activity in these cell lines. Combined treatment with gefitinib and imatinib led to an additional antitumor effect. Each agent induced apoptosis and their combined treatment enhanced apoptosis associated with the down-regulation of antiapoptotic proteins, Bcl-2 and Bcl-xL. Moreover, their combined treatment additionally inhibited the growth of KTC-3 xenografts in nude mice.
CONCLUSIONS: These are the first findings to suggest that both gefitinib and imatinib have antitumor activity against ATC cells and that their combined use has greater activity than either drug alone.
Authors:
Junichi Kurebayashi; Sumiko Okubo; Yutaka Yamamoto; Masahiko Ikeda; Katsuhiro Tanaka; Takemi Otsuki; Hiroshi Sonoo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-25
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  58     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-07-03     Completed Date:  2006-08-24     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  460-70     Citation Subset:  IM    
Affiliation:
Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, 701-0192, Okayama, Japan. kure@med.kawasaki-m.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*,  therapeutic use
Apoptosis / drug effects
Cell Line, Tumor
DNA Primers / genetics
Drug Synergism
Female
Humans
Mice
Piperazines / pharmacology*
Protein-Tyrosine Kinases / antagonists & inhibitors*
Pyrimidines / pharmacology*
Quinazolines / pharmacology*,  therapeutic use
Reverse Transcriptase Polymerase Chain Reaction
Thyroid Neoplasms / drug therapy
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/DNA Primers; 0/Piperazines; 0/Pyrimidines; 0/Quinazolines; BKJ8M8G5HI/imatinib; EC 2.7.10.1/Protein-Tyrosine Kinases; S65743JHBS/gefitinib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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