Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most lethal human cancers with a median survival of 6 months. The inhibition of epidermal growth factor receptor (EGFR) alone, or with VEGF receptor 2 (VEGFR2), represents an attractive approach for treatment of ATC. Several reports have examined agents that target these receptors. However, with the misidentification of as many as 60% of all commonly used ATC cell lines, the significance of these past findings is unclear.Experimental Design: Cell lines authenticated by short tandem repeat profiling were selected to establish xenograft tumors in an orthotopic murine model of ATC. These mice were then treated with vandetanib to evaluate its effects on ATC tumor growth. Dynamic contrast-enhanced (DCE) MRI was utilized to measure the impact of vandetanib on tumor vasculature.Results: Vandetanib inhibited tumor growth of the ATC cell lines Hth83 and 8505C in vivo by 69.3% (P < 0.001) and 66.6% (P < 0.05), respectively, when compared with control. Significant decreases in vascular permeability (P < 0.01) and vascular volume fraction (P < 0.05) were detected by DCE-MRI in the orthotopic xenograft tumors after 1 week of treatment with vandetanib as compared with control.Conclusion: The inhibition of EGFR and VEGFR2 by vandetanib and its tremendous in vivo antitumor activity against ATC make it an attractive candidate for further preclinical and clinical development for the treatment of this particularly virulent cancer, which remains effectively untreatable. Vandetanib disrupts angiogenesis and DCE-MRI is an effective method to quantify changes in vascular function in vivo. Clin Cancer Res; 17(8); 2281-91. Ó2011 AACR.
Objective
To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the VEGFR (DC101) and the EGFR (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of oral tongue (SCCOT).
Design
In vivo study.
Subjects
8- to 12- week-old male athymic nude mice.
Intervention
To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase-expressing human 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, all given twice per week for 4 weeks. The in vivo anti-tumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunoflourescent staining were performed.
Results
At the conclusion of the treatment period, the average tumor volumes in the cetuximab alone and the DC101 plus cextuximab treatment groups had decreased significantly compared with those that received control (68%, P=0.002 and 84%, P=0.0003 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=0.003).
Conclusion
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 stategy against metastatic SCCOT and warrants further pre-clinical trials.
We hereby report the case of a patient with optic nerve sheath meningioma (ONSM), whose diagnosis and multidisciplinary management was guided by the use of Gallium-68 (68Ga)-labeled dodecanetetraacetic acid-tyrosine-3-octreotate (DOTATATE) positron emission tomography (PET)/computed tomography (CT) scan. We briefly review the diagnosis and management of ONSM, and review the literature on the role and current status of nuclear imaging with somatostatin receptor ligands in the non-invasive diagnosis and management of meningiomas.
Background
The local-regional failure of advanced oral squamous cell carcinoma (OSCC) after surgery results from the re-growth of residual tumor cells that may be stimulated by epidermal growth factor receptor (EGFR) ligands during the wound-healing process.
Methods
The level of EGFR ligands in human drain fluids from OSCC resection and remote flap donor site were determined. A mouse model of microscopic residual OSCC was established and treated with cetuximab to measure tumor growth, survival, and cervical lymph node metastases. A mouse model of wound-healing was also established to assess the effect of an EGFR antibody on the wound-healing process.
Results
EGFR ligands are found in sites from OSCC resection. EGFR targeted therapy can delay tumor re-growth in a microscopic residual disease model of OSCC without significant effects on local wound-healing.
Conclusion
These results provide a strong rationale for clinical evaluation of this approach to treat patients with local-regionally advanced OSCC.
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