RGD Reference Report - The effect of combination anti-endothelial growth factor receptor and anti-vascular endothelial growth factor receptor 2 targeted therapy on lymph node metastasis: a study in an orthotopic nude mouse model of squamous cell carcinoma of the oral tongue. - Rat Genome Database

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The effect of combination anti-endothelial growth factor receptor and anti-vascular endothelial growth factor receptor 2 targeted therapy on lymph node metastasis: a study in an orthotopic nude mouse model of squamous cell carcinoma of the oral tongue.

Authors: Sano, D  Choi, S  Milas, ZL  Zhou, G  Galer, CE  Su, YW  Gule, M  Zhao, M  Zhu, Z  Myers, JN 
Citation: Sano D, etal., Arch Otolaryngol Head Neck Surg. 2009 Apr;135(4):411-20. doi: 10.1001/archoto.2009.14.
RGD ID: 8551769
Pubmed: PMID:19380367   (View Abstract at PubMed)
PMCID: PMC2914603   (View Article at PubMed Central)
DOI: DOI:10.1001/archoto.2009.14   (Journal Full-text)

OBJECTIVE: To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the vascular endothelial growth factor receptor (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of the oral tongue (SCCOT). DESIGN: In vivo study. SETTING: A translational research laboratory at a comprehensive cancer center. SUBJECTS: Male athymic nude mice aged 8 to 12 weeks. INTERVENTION: To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone, cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were administered twice per week for 4 weeks. The in vivo antitumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunofluorescent staining were performed. MAIN OUTCOME MEASURES: Tumor size, bioluminescence, animal survival, and percentage of animals with lymph node metastasis. RESULTS: At the conclusion of the treatment period, the mean tumor volumes in the cetuximab alone and the DC101 plus cetuximab groups had decreased significantly compared with those that received the placebo control (68% [P = .002] and 84% [P < .001], respectively). Significant effects of the treatment were also observed in bioluminescence imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower incidence of neck lymph node metastases compared with the control group (P = .003). CONCLUSIONS: Treatment with DC101 plus cetuximab inhibited the growth of SCCOT and decreased the incidence of the neck lymph node metastases in vivo. These results suggest that this combination treatment may be an effective strategy against metastatic SCCOT and warrants further preclinical trials.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Lymphatic Metastasis treatmentISOEgfr (Mus musculus)8551769; 8551769associated with Squamous Cell Carcinoma of the TongueRGD 
Lymphatic Metastasis treatmentIMP 8551769; 8551769associated with Squamous Cell Carcinoma of the TongueRGD 
Lymphatic Metastasis treatmentISOKdr (Mus musculus)8551769; 8551769associated with Squamous Cell Carcinoma of the TongueRGD 
tongue squamous cell carcinoma treatmentISOEgfr (Mus musculus)8551769; 8551769 RGD 
tongue squamous cell carcinoma treatmentIMP 8551769; 8551769 RGD 
tongue squamous cell carcinoma treatmentISOKdr (Mus musculus)8551769; 8551769 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)
Kdr  (kinase insert domain receptor)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)
Kdr  (kinase insert domain protein receptor)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)
KDR  (kinase insert domain receptor)


Additional Information