http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1\
5756027&dopt=Abstract
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=\
15756027&dopt=Abstract>

Clin Cancer Res. 2005 Mar 1;11(5):2008-17.
http://clincancerres.aacrjournals.org/cgi/content/abstract/11/5/2008

Herceptin Down-Regulates HER-2/neu and Vascular Endothelial Growth
Factor Expression and Enhances Taxol-Induced Cytotoxicity of Human
Ewing's Sarcoma Cells In vitro and In vivo.

Guan H, Jia SF, Zhou Z, Stewart J, Kleinerman ES.

Eugenie S. Kleinerman, Division of Pediatrics, Unit 87, University of
Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX
77030. Phone: 713-792-8110; Fax: 713-794-5042; E-mail:
ekleiner@...

Division of Pediatrics and Department of Pathology, University of Texas
M.D. Anderson Cancer Center, Houston, Texas.

We have previously shown that high levels of HER-2/neu protein were
overexpressed in human Ewing's sarcoma cells (TC71, SK-ES1) relative to
normal human osteoblasts. The purpose of this study was to determine
whether herceptin alone or in combination with chemotherapeutic agents
could inhibit the growth of Ewing's sarcoma in vitro and in vivo.
Western blot analysis showed that the protein levels of HER-2/neu were
decreased following herceptin treatment. Cell growth was also inhibited
by herceptin in a dose-dependent manner with an IC(50) of 4 mg/mL in
TC71 and SK-ES1 cell line, whereas human immunoglobin had no effect.
Northern blot and ELISA showed the RNA expression and protein levels of
vascular endothelial growth factor were also inhibited by herceptin
treatment with no alteration in HIF-1alpha protein and topoisomerase
IIalpha expression. Furthermore, Ewing's sarcoma tumor growth was
significantly delayed by 100 mg/kg herceptin treatment in our Ewing's
sarcoma xenograft mouse model. Combining taxol with herceptin resulted
in additive cytotoxicity, whereas herceptin-etoposide, doxorubicin, and
9-nitrocamptothecin combinations did not. Taxol-herceptin enhanced
growth inhibition in TC71 cells in vitro compared with either agent
alone. Ewing's sarcoma growth was also delayed in vivo and mean tumor
size was significantly lower in mice treated with herceptin plus taxol
than in those receiving taxol or herceptin alone. These data suggest
that herceptin in combination with taxol may be a therapeutic option in
the treatment of Ewing's sarcoma.

PMID: 15756027 [PubMed - in process]