PMID- 17031648
OWN - NLM
STAT- MEDLINE
DCOM- 20070515
LR  - 20151119
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 59
IP  - 6
DP  - 2007 May
TI  - Antitumor activity of trastuzumab in combination with chemotherapy in human 
      gastric cancer xenograft models.
PG  - 795-805
AB  - PURPOSE: To clarify the antitumor activity of trastuzumab and its potential as an 
      effective treatment for gastric cancer patients. METHODS: Levels of HER2 
      expression in tumor tissues of gastric cancer cell lines were examined using 
      immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and mRNA 
      quantification. Efficacy of trastuzumab was examined as a single agent or in 
      combination with chemotherapeutic agents widely used clinically for gastric 
      cancers in HER2-overexpressing human gastric cancer xenograft models. RESULTS: 
      Two of nine human gastric cancer xenograft models, NCI-N87 and 4-1ST, showed 
      overexpression of HER2 mRNA and protein by IHC (HercepTest) and HER2 gene 
      amplification by FISH (Pathvysion). HER2 protein showed potent staining in 
      peripheral membranes, similar to the staining pattern of breast cancer. FISH 
      scores were also comparable to those of breast cancer models. Trastuzumab as a 
      single agent inhibited the tumor growth in both of the HER2-overexpressing models 
      but not in the HER2-negative models, GXF97 and MKN-45. In any combination with 
      capecitabine, cisplatin, irinotecan, docetaxel, or paclitaxel, trastuzumab showed 
      more potent antitumor activity than the anticancer agents alone. A three-drug 
      combination of capecitabine, cisplatin, and trastuzumab showed remarkable tumor 
      growth inhibition. In NCI-N87 in vitro, trastuzumab showed direct 
      antiproliferative activity according to cell count or crystal violet dying, and 
      showed indirect antitumor activity such as antibody-dependent cellular 
      cytotoxicity. CONCLUSION: The antitumor activity of trastuzumab observed in human 
      gastric cancer models warrants consideration of its use in clinical treatment 
      regimens for human gastric cancer as a single agent or a combination drug with 
      various chemotherapeutic agents.
FAU - Fujimoto-Ouchi, Kaori
AU  - Fujimoto-Ouchi K
AD  - Product Research Department, Kamakura Research Center, Chugai Pharmaceuticals 
      Co., Ltd, 200 Kajiwara Kamakura, Kanagawa, 247-8530, Japan. 
      ohuchikor@chugai-pharm.co.jp
FAU - Sekiguchi, Fumiko
AU  - Sekiguchi F
FAU - Yasuno, Hideyuki
AU  - Yasuno H
FAU - Moriya, Yoichiro
AU  - Moriya Y
FAU - Mori, Kazushige
AU  - Mori K
FAU - Tanaka, Yutaka
AU  - Tanaka Y
LA  - eng
PT  - Journal Article
DEP - 20061010
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Cell Proliferation/drug effects
MH  - Drug Evaluation, Preclinical/methods
MH  - Humans
MH  - Mice
MH  - Receptor, ErbB-2/metabolism
MH  - Stomach Neoplasms/*drug therapy/metabolism
MH  - Trastuzumab
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
EDAT- 2006/10/13 09:00
MHDA- 2007/05/16 09:00
CRDT- 2006/10/13 09:00
PHST- 2006/05/03 00:00 [received]
PHST- 2006/08/15 00:00 [accepted]
PHST- 2006/10/13 09:00 [pubmed]
PHST- 2007/05/16 09:00 [medline]
PHST- 2006/10/13 09:00 [entrez]
AID - 10.1007/s00280-006-0337-z [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2007 May;59(6):795-805. doi: 
      10.1007/s00280-006-0337-z. Epub 2006 Oct 10.