PMID- 16995874
OWN - NLM
STAT- MEDLINE
DCOM- 20061219
LR  - 20220325
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 97
IP  - 12
DP  - 2006 Dec
TI  - ZD6474 induces growth arrest and apoptosis of GIST-T1 cells, which is enhanced by 
      concomitant use of sunitinib.
PG  - 1404-9
AB  - ZD6474 (Zactima, AstraZeneca, Macclesfield, UK) is an orally available, 
      small-molecule inhibitor of vascular endothelial growth factor receptor-2 and 
      epidermal growth factor receptor tyrosine kinases, with additional activity 
      versus rearranged during transfection (RET). This study explored the effect of 
      ZD6474 in gastrointestinal stromal tumor-T1 (GIST-T1) cells that possess a gain 
      of function mutation in exon 11 of the c-KIT gene. ZD6474 induced growth arrest 
      and apoptosis of GIST-T1 cells in association with blockade of c-Kit and its 
      downstream effectors, including Akt and extracellular signal-regulated kinase 
      (ERK). ZD6474 treatment also blocked the mammalian target of rapamycin (mTOR), 
      which lies downstream of Akt and ERK. Interestingly, when ZD6474 was combined 
      with sunitinib (SU11248; Sutent, Pfizer, Kalamazoo, MI, USA), a class III and V 
      receptor tyrosine kinase inhibitor, the ZD6474-mediated growth inhibition was 
      potentiated in association with further down-regulation of the mTOR targets 
      p-p70S6K and p-4E-BP-1. The combination of ZD6474 and sunitinib should be 
      investigated further.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Biochemistry and Molecular Biology, Peking University Health 
      Science Center, Beijing 100083, China.
FAU - Ikezoe, Takayuki
AU  - Ikezoe T
FAU - Nishioka, Chie
AU  - Nishioka C
FAU - Taguchi, Takahiro
AU  - Taguchi T
FAU - Zhu, Wei-Guo
AU  - Zhu WG
FAU - Koeffler, H Phillip
AU  - Koeffler HP
FAU - Taguchi, Hirokuni
AU  - Taguchi H
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060921
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Indoles)
RN  - 0 (Phosphoproteins)
RN  - 0 (Piperidines)
RN  - 0 (Pyrroles)
RN  - 0 (Quinazolines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - V99T50803M (Sunitinib)
RN  - YO460OQ37K (vandetanib)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Cycle Proteins
MH  - Cell Proliferation/*drug effects
MH  - Drug Therapy, Combination
MH  - Gastrointestinal Stromal Tumors/*drug therapy/metabolism
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Piperidines/*pharmacology
MH  - Protein Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Pyrroles/*pharmacology
MH  - Quinazolines/*pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Sunitinib
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Cells, Cultured
EDAT- 2006/09/26 09:00
MHDA- 2006/12/21 09:00
CRDT- 2006/09/26 09:00
PHST- 2006/09/26 09:00 [pubmed]
PHST- 2006/12/21 09:00 [medline]
PHST- 2006/09/26 09:00 [entrez]
AID - CAS325 [pii]
AID - 10.1111/j.1349-7006.2006.00325.x [doi]
PST - ppublish
SO  - Cancer Sci. 2006 Dec;97(12):1404-9. doi: 10.1111/j.1349-7006.2006.00325.x. Epub 
      2006 Sep 21.