PMID- 9989823
OWN - NLM
STAT- MEDLINE
DCOM- 19990316
LR  - 20181201
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 3
DP  - 1999 Jan 21
TI  - Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a 
      human-mouse chimeric anti-EGF receptor mAb C225.
PG  - 731-8
AB  - Overexpression of epidermal growth factor (EGF) receptor and HER2 (p185neu) may 
      both contribute to the growth of human cancers. A humanized anti-HER2 monoclonal 
      antibody (mAb) 4D5 and a human-mouse chimeric anti-EGF receptor mAb C225 are 
      currently being investigated in clinical trials for their anti-tumor activities. 
      In the present study, we have examined the effect of concurrent treatment of OVCA 
      420 human ovarian cancer cells with mAb C225 and mAb 4D5. Exposure of OVCA420 
      cells to saturating concentrations of C225 (20 nM) for 7 days resulted in 40-50% 
      growth inhibition, and exposure to 20 nM mAb 4D5 also resulted in 30-40% growth 
      inhibition. The growth inhibition of OVCA420 cells by mAb C225 or 4D5 was 
      associated with an increased G1 cell population; an increased level of a 
      cyclin-dependent kinase (CDK) inhibitor p27Kip1 with increased association of 
      p27kip1 with CDK2, CDK4 and CDK6; and decreased activities of these CDKs. 
      Combination treatment with concurrent exposure to mAbs C225 and 4D5 resulted in 
      additive anti-proliferative effects on these cells, which was accompanied by 
      enhanced G1 cell distribution, a greater increase in the levels of p27Kip1 and a 
      greater decrease in the activities of CDK kinases. The anti-proliferative effects 
      and related changes in cell cycle regulators induced by mAb 4D5, mAb C225 or the 
      combination of the two mAbs could be reversed by concurrent exposure to exogenous 
      EGF. Our data suggest the potential fruitful cooperation of anti-EGF receptor mAb 
      and anti-HER2 mAb in the treatment of human cancers stimulated by EGF receptor 
      and HER2 signals.
FAU - Ye, D
AU  - Ye D
AD  - The University of Texas, M.D. Anderson Cancer Center, Houston 77030-4009, USA.
FAU - Mendelsohn, J
AU  - Mendelsohn J
FAU - Fan, Z
AU  - Fan Z
LA  - eng
GR  - CA42060/CA/NCI NIH HHS/United States
GR  - CA68425/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cdkn1b protein, mouse)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/metabolism/pharmacology
MH  - *Cell Cycle Proteins
MH  - Cell Division
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclin-Dependent Kinases/antagonists & inhibitors
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/metabolism/pharmacology
MH  - ErbB Receptors/immunology/*metabolism
MH  - Female
MH  - G1 Phase
MH  - Growth Inhibitors/metabolism/pharmacology
MH  - Humans
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - Ovarian Neoplasms/*therapy
MH  - Receptor, ErbB-2/immunology/*metabolism
MH  - Recombinant Fusion Proteins
MH  - Tumor Cells, Cultured
MH  - *Tumor Suppressor Proteins
EDAT- 1999/02/16 00:00
MHDA- 1999/02/16 00:01
CRDT- 1999/02/16 00:00
PHST- 1999/02/16 00:00 [pubmed]
PHST- 1999/02/16 00:01 [medline]
PHST- 1999/02/16 00:00 [entrez]
AID - 10.1038/sj.onc.1202319 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jan 21;18(3):731-8. doi: 10.1038/sj.onc.1202319.